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Taheri M, Tehrani HA, Dehghani S, Alibolandi M, Arefian E, Ramezani M. Nanotechnology and bioengineering approaches to improve the potency of mesenchymal stem cell as an off-the-shelf versatile tumor delivery vehicle. Med Res Rev 2024; 44:1596-1661. [PMID: 38299924 DOI: 10.1002/med.22023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 11/28/2023] [Accepted: 01/10/2024] [Indexed: 02/02/2024]
Abstract
Targeting actionable mutations in oncogene-driven cancers and the evolution of immuno-oncology are the two prominent revolutions that have influenced cancer treatment paradigms and caused the emergence of precision oncology. However, intertumoral and intratumoral heterogeneity are the main challenges in both fields of precision cancer treatment. In other words, finding a universal marker or pathway in patients suffering from a particular type of cancer is challenging. Therefore, targeting a single hallmark or pathway with a single targeted therapeutic will not be efficient for fighting against tumor heterogeneity. Mesenchymal stem cells (MSCs) possess favorable characteristics for cellular therapy, including their hypoimmune nature, inherent tumor-tropism property, straightforward isolation, and multilineage differentiation potential. MSCs can be loaded with various chemotherapeutics and oncolytic viruses. The combination of these intrinsic features with the possibility of genetic manipulation makes them a versatile tumor delivery vehicle that can be used for in vivo selective tumor delivery of various chemotherapeutic and biological therapeutics. MSCs can be used as biofactory for the local production of chemical or biological anticancer agents at the tumor site. MSC-mediated immunotherapy could facilitate the sustained release of immunotherapeutic agents specifically at the tumor site, and allow for the achievement of therapeutic concentrations without the need for repetitive systemic administration of high therapeutic doses. Despite the enthusiasm evoked by preclinical studies that used MSC in various cancer therapy approaches, the translation of MSCs into clinical applications has faced serious challenges. This manuscript, with a critical viewpoint, reviewed the preclinical and clinical studies that have evaluated MSCs as a selective tumor delivery tool in various cancer therapy approaches, including gene therapy, immunotherapy, and chemotherapy. Then, the novel nanotechnology and bioengineering approaches that can improve the potency of MSC for tumor targeting and overcoming challenges related to their low localization at the tumor sites are discussed.
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Affiliation(s)
- Mojtaba Taheri
- Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Hossein Abdul Tehrani
- Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Sadegh Dehghani
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mona Alibolandi
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ehsan Arefian
- Department of Microbiology, School of Biology, College of Science, University of Tehran, Tehran, Iran
- Pediatric Cell and Gene Therapy Research Center, Gene, Cell & Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Ramezani
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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2
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Ijaz M, Aslam B, Hasan I, Ullah Z, Roy S, Guo B. Cell membrane-coated biomimetic nanomedicines: productive cancer theranostic tools. Biomater Sci 2024; 12:863-895. [PMID: 38230669 DOI: 10.1039/d3bm01552a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2024]
Abstract
As the second-leading cause of human death, cancer has drawn attention in the area of biomedical research and therapy from all around the world. Certainly, the development of nanotechnology has made it possible for nanoparticles (NPs) to be used as a carrier for delivery systems in the treatment of tumors. This is a biomimetic approach established to craft remedial strategies comprising NPs cloaked with membrane obtained from various natural cells like blood cells, bacterial cells, cancer cells, etc. Here we conduct an in-depth exploration of cell membrane-coated NPs (CMNPs) and their extensive array of applications including drug delivery, vaccination, phototherapy, immunotherapy, MRI imaging, PET imaging, multimodal imaging, gene therapy and a combination of photothermal and chemotherapy. This review article provides a thorough summary of the most recent developments in the use of CMNPs for the diagnosis and treatment of cancer. It critically assesses the state of research while recognizing significant accomplishments and innovations. Additionally, it indicates ongoing problems in clinical translation and associated queries that warrant deeper research. By doing so, this study encourages creative thinking for future projects in the field of tumor therapy using CMNPs while also educating academics on the present status of CMNP research.
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Affiliation(s)
- Muhammad Ijaz
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen-518055, China.
- Institute of Microbiology, Government College University Faisalabad Pakistan, Pakistan
| | - Bilal Aslam
- Institute of Microbiology, Government College University Faisalabad Pakistan, Pakistan
| | - Ikram Hasan
- School of Biomedical Engineering, Medical School, Shenzhen University, Shenzhen, Guangdong, 518060, China
| | - Zia Ullah
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen-518055, China.
| | - Shubham Roy
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen-518055, China.
| | - Bing Guo
- School of Science, Shenzhen Key Laboratory of Flexible Printed Electronics Technology, Shenzhen Key Laboratory of Advanced Functional Carbon Materials Research and Comprehensive Application, Harbin Institute of Technology, Shenzhen-518055, China.
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3
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Han H, Chen BT, Liu Y, Wang Y, Xing L, Wang H, Zhou TJ, Jiang HL. Engineered stem cell-based strategy: A new paradigm of next-generation stem cell product in regenerative medicine. J Control Release 2024; 365:981-1003. [PMID: 38123072 DOI: 10.1016/j.jconrel.2023.12.024] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 12/06/2023] [Accepted: 12/16/2023] [Indexed: 12/23/2023]
Abstract
Stem cells have garnered significant attention in regenerative medicine owing to their abilities of multi-directional differentiation and self-renewal. Despite these encouraging results, the market for stem cell products yields limited, which is largely due to the challenges faced to the safety and viability of stem cells in vivo. Besides, the fate of cells re-infusion into the body unknown is also a major obstacle to stem cell therapy. Actually, both the functional protection and the fate tracking of stem cells are essential in tissue homeostasis, repair, and regeneration. Recent studies have utilized cell engineering techniques to modify stem cells for enhancing their treatment efficiency or imparting them with novel biological capabilities, in which advances demonstrate the immense potential of engineered cell therapy. In this review, we proposed that the "engineered stem cells" are expected to represent the next generation of stem cell therapies and reviewed recent progress in this area. We also discussed potential applications of engineered stem cells and highlighted the most common challenges that must be addressed. Overall, this review has important guiding significance for the future design of new paradigms of stem cell products to improve their therapeutic efficacy.
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Affiliation(s)
- Han Han
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Bi-Te Chen
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Yang Liu
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Yi Wang
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China
| | - Lei Xing
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China; College of Pharmacy, Yanbian University, Yanji 133002, China
| | - Hui Wang
- Department of Endocrinology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
| | - Tian-Jiao Zhou
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China.
| | - Hu-Lin Jiang
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China; College of Pharmacy, Yanbian University, Yanji 133002, China.
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4
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Xiao Y, Xu RH, Dai Y. Nanoghosts: Harnessing Mesenchymal Stem Cell Membrane for Construction of Drug Delivery Platforms Via Optimized Biomimetics. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2024; 20:e2304824. [PMID: 37653618 DOI: 10.1002/smll.202304824] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 08/10/2023] [Indexed: 09/02/2023]
Abstract
Mesenchymal stem cells (MSCs) are becoming hotspots for application in disease therapies recently, combining with biomaterials and drug delivery system. A major advantage of MSCs applied in drug delivery system is that these cells enable specific targeting and releasing of cargos to the disease sites. However, the potential tumor tropic effects of MSCs raised concerns on biosafety. To solve this problem, there are emerging methods of isolating cell membranes and developing nanoformulations to perform drug delivery, which avoids concerns on biosafety without disturbing the membrane functions of specific polarizing and locating. These cargoes are so called "nanoghosts." This review article summarizes the current applications of nanoghosts, the promising potential of MSCs to be applied in membrane isolation and nanoghost construction, and possible approaches to develop better drug delivery system harnessing from MSC ghost cell membranes.
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Affiliation(s)
- Yuan Xiao
- Faculty of Health Sciences and MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, 999078, China
| | - Ren-He Xu
- Faculty of Health Sciences and MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, 999078, China
| | - Yunlu Dai
- Faculty of Health Sciences and MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, 999078, China
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Fatima F, Chourasiya NK, Mishra M, Kori S, Pathak S, Das R, Kashaw V, Iyer AK, Kashaw SK. Curcumin and its Derivatives Targeting Multiple Signaling Pathways to Elicit Anticancer Activity: A Comprehensive Perspective. Curr Med Chem 2024; 31:3668-3714. [PMID: 37221681 DOI: 10.2174/0929867330666230522144312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 03/23/2023] [Accepted: 04/07/2023] [Indexed: 05/25/2023]
Abstract
The uncontrolled growth and spread of aberrant cells characterize the group of disorders known as cancer. According to GLOBOCAN 2022 analysis of cancer patients in either developed countries or developing countries the main concern cancers are breast cancer, lung cancer, and liver cancer which may rise eventually. Natural substances with dietary origins have gained interest for their low toxicity, anti-inflammatory, and antioxidant effects. The evaluation of dietary natural products as chemopreventive and therapeutic agents, the identification, characterization, and synthesis of their active components, as well as the enhancement of their delivery and bioavailability, have all received significant attention. Thus, the treatment strategy for concerning cancers must be significantly evaluated and may include the use of phytochemicals in daily lifestyle. In the present perspective, we discussed one of the potent phytochemicals, that has been used over the past few decades known as curcumin as a panacea drug of the "Cure-all" therapy concept. In our review firstly we included exhausted data from in vivo and in vitro studies on breast cancer, lung cancer, and liver cancer which act through various cancer-targeting pathways at the molecular level. Now, the second is the active constituent of turmeric known as curcumin and its derivatives are enlisted with their targeted protein in the molecular docking studies, which help the researchers design and synthesize new curcumin derivatives with respective implicated molecular and cellular activity. However, curcumin and its substituted derivatives still need to be investigated with unknown targeting mechanism studies in depth.
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Affiliation(s)
- Firdous Fatima
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Nikhil Kumar Chourasiya
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Mitali Mishra
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Shivam Kori
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Sandhya Pathak
- Department of Chemistry, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Ratnesh Das
- Department of Chemistry, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Varsha Kashaw
- Sagar Institute of Pharmaceutical Sciences, Sagar (M.P.), India
| | - Arun K Iyer
- Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan, USA
- Molecular Imaging Program, Karmanos Cancer Institute, Detroit, Michigan, USA
| | - Sushil Kumar Kashaw
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
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Shams F, Pourjabbar B, Hashemi N, Farahmandian N, Golchin A, Nuoroozi G, Rahimpour A. Current progress in engineered and nano-engineered mesenchymal stem cells for cancer: From mechanisms to therapy. Biomed Pharmacother 2023; 167:115505. [PMID: 37716113 DOI: 10.1016/j.biopha.2023.115505] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2023] [Revised: 09/11/2023] [Accepted: 09/12/2023] [Indexed: 09/18/2023] Open
Abstract
Mesenchymal stem cells (MSCs), as self-renewing multipotent stromal cells, have been considered promising agents for cancer treatment. A large number of studies have demonstrated the valuable properties of MSC-based treatment, such as low immunogenicity and intrinsic tumor-trophic migratory properties. To enhance the potency of MSCs for therapeutic purposes, equipping MSCs with targeted delivery functions using genetic engineering is highly beneficial. Genetically engineered MSCs can express tumor suppressor agents such as pro-apoptotic, anti-proliferative, anti-angiogenic factors and act as ideal delivery vehicles. MSCs can also be loaded with nanoparticle drugs for increased efficacy and externally moderated targeting. Moreover, exosomes secreted by MSCs have important physiological properties, so they can contribute to intercellular communication and transfer cargo into targeted tumor cells. The precise role of genetically modified MSCs in tumor environments is still up for debate, but the beginning of clinical trials has been confirmed by promising results from preclinical investigations of MSC-based gene therapy for a wide range of malignancies. This review highlights the advanced techniques of engineering/nano-engineering and MSC-derived exosomes in tumor-targeted therapy.
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Affiliation(s)
- Forough Shams
- Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, 1968917313 Tehran, Iran
| | - Bahareh Pourjabbar
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nader Hashemi
- Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, 1968917313 Tehran, Iran
| | - Navid Farahmandian
- Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Golchin
- Cellular & Molecular Research Center, Cellular & Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia 57157993313, Iran; Department of Clinical Biochemistry & Applied Cell Sciences, School of Medicine, Urmia University of Medical Sciences, Urmia 57157993313, Islamic Republic of Iran
| | - Ghader Nuoroozi
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azam Rahimpour
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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7
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Su Y, Huang T, Sun H, Lin R, Zheng X, Bian Q, Zhang J, Chen S, Wu H, Xu D, Zhang T, Gao J. High Targeting Specificity toward Pulmonary Inflammation Using Mesenchymal Stem Cell-Hybrid Nanovehicle for an Efficient Inflammation Intervention. Adv Healthc Mater 2023; 12:e2300376. [PMID: 37161587 DOI: 10.1002/adhm.202300376] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 05/05/2023] [Indexed: 05/11/2023]
Abstract
Pulmonary inflammation is one of the most reported tissue inflammations in clinic. Successful suppression of inflammation is vital to prevent further inevitably fatal lung degeneration. Glucocorticoid hormone, such as methylprednisolone (MP), is the most applied strategy to control the inflammatory progression yet faces the challenge of systemic side effects caused by the requirement of large-dosage and frequent administration. Highly efficient delivery of MP specifically targeted to inflammatory lung sites may overcome this challenge. Therefore, the present study develops an inflammation-targeted biomimetic nanovehicle, which hybridizes the cell membrane of mesenchymal stem cell with liposome, named as MSCsome. This hybrid nanovehicle shows the ability of high targeting specificity toward inflamed lung cells, due to both the good lung endothelium penetration and the high uptake by inflamed lung cells. Consequently, a single-dose administration of this MP-loaded hybrid nanovehicle achieves a prominent treatment of lipopolysaccharide-induced lung inflammation, and negligible treatment-induced side effects are observed. The present study provides a powerful inflammation-targeted nanovehicle using biomimetic strategy to solve the current challenges of targeted inflammation intervention.
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Affiliation(s)
- Yuanqin Su
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
- Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China
| | - Ting Huang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Hao Sun
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Ruyi Lin
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Xixi Zheng
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
- Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China
| | - Qiong Bian
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Jinsong Zhang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Shihan Chen
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
- Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China
| | - Honghui Wu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
- Jinhua Institute of Zhejiang University, Zhejiang University, Jinhua, 321002, China
| | - Donghang Xu
- Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China
| | - Tianyuan Zhang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
- Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China
- Jinhua Institute of Zhejiang University, Zhejiang University, Jinhua, 321002, China
| | - Jianqing Gao
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
- Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, 310058, Hangzhou, China
- Jinhua Institute of Zhejiang University, Zhejiang University, Jinhua, 321002, China
- Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China
- Cancer Center, Zhejiang University, Hangzhou, 310058, China
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Slama Y, Ah-Pine F, Khettab M, Arcambal A, Begue M, Dutheil F, Gasque P. The Dual Role of Mesenchymal Stem Cells in Cancer Pathophysiology: Pro-Tumorigenic Effects versus Therapeutic Potential. Int J Mol Sci 2023; 24:13511. [PMID: 37686315 PMCID: PMC10488262 DOI: 10.3390/ijms241713511] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 08/29/2023] [Accepted: 08/30/2023] [Indexed: 09/10/2023] Open
Abstract
Mesenchymal stem/stromal cells (MSCs) are multipotent cells involved in numerous physiological events, including organogenesis, the maintenance of tissue homeostasis, regeneration, or tissue repair. MSCs are increasingly recognized as playing a major, dual, and complex role in cancer pathophysiology through their ability to limit or promote tumor progression. Indeed, these cells are known to interact with the tumor microenvironment, modulate the behavior of tumor cells, influence their functions, and promote distant metastasis formation through the secretion of mediators, the regulation of cell-cell interactions, and the modulation of the immune response. This dynamic network can lead to the establishment of immunoprivileged tissue niches or the formation of new tumors through the proliferation/differentiation of MSCs into cancer-associated fibroblasts as well as cancer stem cells. However, MSCs exhibit also therapeutic effects including anti-tumor, anti-proliferative, anti-inflammatory, or anti-oxidative effects. The therapeutic interest in MSCs is currently growing, mainly due to their ability to selectively migrate and penetrate tumor sites, which would make them relevant as vectors for advanced therapies. Therefore, this review aims to provide an overview of the double-edged sword implications of MSCs in tumor processes. The therapeutic potential of MSCs will be reviewed in melanoma and lung cancers.
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Affiliation(s)
- Youssef Slama
- Unité de Recherche Études Pharmaco-Immunologiques (EPI), Université de La Réunion, CHU de La Réunion, Allée des Topazes, 97400 Saint-Denis, La Réunion, France; (F.A.-P.); (M.K.); (P.G.)
- Service de Radiothérapie, Clinique Sainte-Clotilde, Groupe Clinifutur, 127 Route de Bois de Nèfles, 97400 Saint-Denis, La Réunion, France; (M.B.); (F.D.)
- Laboratoire Interdisciplinaire de Recherche en Santé (LIRS), RunResearch, Clinique Sainte-Clotilde, 127 Route de Bois de Nèfles, 97400 Saint-Denis, La Réunion, France;
| | - Franck Ah-Pine
- Unité de Recherche Études Pharmaco-Immunologiques (EPI), Université de La Réunion, CHU de La Réunion, Allée des Topazes, 97400 Saint-Denis, La Réunion, France; (F.A.-P.); (M.K.); (P.G.)
- Service d’Anatomie et Cytologie Pathologiques, CHU de La Réunion sites SUD—Saint-Pierre, Avenue François Mitterrand, 97448 Saint-Pierre Cedex, La Réunion, France
| | - Mohamed Khettab
- Unité de Recherche Études Pharmaco-Immunologiques (EPI), Université de La Réunion, CHU de La Réunion, Allée des Topazes, 97400 Saint-Denis, La Réunion, France; (F.A.-P.); (M.K.); (P.G.)
- Service d’Oncologie Médicale, CHU de La Réunion sites SUD—Saint-Pierre, Avenue François Mitterrand, 97448 Saint-Pierre Cedex, La Réunion, France
| | - Angelique Arcambal
- Laboratoire Interdisciplinaire de Recherche en Santé (LIRS), RunResearch, Clinique Sainte-Clotilde, 127 Route de Bois de Nèfles, 97400 Saint-Denis, La Réunion, France;
| | - Mickael Begue
- Service de Radiothérapie, Clinique Sainte-Clotilde, Groupe Clinifutur, 127 Route de Bois de Nèfles, 97400 Saint-Denis, La Réunion, France; (M.B.); (F.D.)
- Laboratoire Interdisciplinaire de Recherche en Santé (LIRS), RunResearch, Clinique Sainte-Clotilde, 127 Route de Bois de Nèfles, 97400 Saint-Denis, La Réunion, France;
| | - Fabien Dutheil
- Service de Radiothérapie, Clinique Sainte-Clotilde, Groupe Clinifutur, 127 Route de Bois de Nèfles, 97400 Saint-Denis, La Réunion, France; (M.B.); (F.D.)
- Laboratoire Interdisciplinaire de Recherche en Santé (LIRS), RunResearch, Clinique Sainte-Clotilde, 127 Route de Bois de Nèfles, 97400 Saint-Denis, La Réunion, France;
| | - Philippe Gasque
- Unité de Recherche Études Pharmaco-Immunologiques (EPI), Université de La Réunion, CHU de La Réunion, Allée des Topazes, 97400 Saint-Denis, La Réunion, France; (F.A.-P.); (M.K.); (P.G.)
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9
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Zeng S, Tang Q, Xiao M, Tong X, Yang T, Yin D, Lei L, Li S. Cell membrane-coated nanomaterials for cancer therapy. Mater Today Bio 2023; 20:100633. [PMID: 37128288 PMCID: PMC10148189 DOI: 10.1016/j.mtbio.2023.100633] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 04/01/2023] [Accepted: 04/09/2023] [Indexed: 05/03/2023] Open
Abstract
With the development of nanotechnology, nanoparticles have emerged as a delivery carrier for tumor drug therapy, which can improve the therapeutic effect by increasing the stability and solubility and prolonging the half-life of drugs. However, nanoparticles are foreign substances for humans, are easily cleared by the immune system, are less targeted to tumors, and may even be toxic to the body. As a natural biological material, cell membranes have unique biological properties, such as good biocompatibility, strong targeting ability, the ability to evade immune surveillance, and high drug-carrying capacity. In this article, we review cell membrane-coated nanoparticles (CMNPs) and their applications to tumor therapy. First, we briefly describe CMNP characteristics and applications. Second, we present the characteristics and advantages of different cell membranes as well as nanoparticles, provide a brief description of the process of CMNPs, discuss the current status of their application to tumor therapy, summarize their shortcomings for use in cancer therapy, and propose future research directions. This review summarizes the research progress on CMNPs in cancer therapy in recent years and assesses remaining problems, providing scholars with new ideas for future research on CMNPs in tumor therapy.
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Affiliation(s)
- Shiying Zeng
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Qinglai Tang
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Minna Xiao
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Xinying Tong
- Department of Hemodialysis, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Tao Yang
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Danhui Yin
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Lanjie Lei
- State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210096, China
| | - Shisheng Li
- Department of Otorhinolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
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Jiang Z, Xu Y, Fu M, Zhu D, Li N, Yang G. Genetically modified cell spheroids for tissue engineering and regenerative medicine. J Control Release 2023; 354:588-605. [PMID: 36657601 DOI: 10.1016/j.jconrel.2023.01.033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2022] [Revised: 01/11/2023] [Accepted: 01/12/2023] [Indexed: 01/21/2023]
Abstract
Cell spheroids offer cell-to-cell interactions and show advantages in survival rate and paracrine effect to solve clinical and biomedical inquiries ranging from tissue engineering and regenerative medicine to disease pathophysiology. Therefore, cell spheroids are ideal vehicles for gene delivery. Genetically modified spheroids can enhance specific gene expression to promote tissue regeneration. Gene deliveries to cell spheroids are via viral vectors or non-viral vectors. Some new technologies like CRISPR/Cas9 also have been used in genetically modified methods to deliver exogenous gene to the host chromosome. It has been shown that genetically modified cell spheroids had the potential to differentiate into bone, cartilage, vascular, nerve, cardiomyocytes, skin, and skeletal muscle as well as organs like the liver to replace the diseased organ in the animal and pre-clinical trials. This article reviews the recent articles about genetically modified spheroid cells and explains the fabrication, applications, development timeline, limitations, and future directions of genetically modified cell spheroid.
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Affiliation(s)
- Zhiwei Jiang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310000, China
| | - Yi Xu
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310000, China
| | - Mengdie Fu
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310000, China
| | - Danji Zhu
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310000, China
| | - Na Li
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310000, China
| | - Guoli Yang
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310000, China.
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11
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Zhang W, Huang X. Stem cell membrane-camouflaged targeted delivery system in tumor. Mater Today Bio 2022; 16:100377. [PMID: 35967738 PMCID: PMC9364095 DOI: 10.1016/j.mtbio.2022.100377] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2022] [Revised: 07/17/2022] [Accepted: 07/19/2022] [Indexed: 02/06/2023] Open
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12
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Heris RM, Shirvaliloo M, Abbaspour-Aghdam S, Hazrati A, Shariati A, Youshanlouei HR, Niaragh FJ, Valizadeh H, Ahmadi M. The potential use of mesenchymal stem cells and their exosomes in Parkinson's disease treatment. Stem Cell Res Ther 2022; 13:371. [PMID: 35902981 PMCID: PMC9331055 DOI: 10.1186/s13287-022-03050-4] [Citation(s) in RCA: 51] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Accepted: 07/17/2022] [Indexed: 12/13/2022] Open
Abstract
Parkinson's disease (PD) is the second most predominant neurodegenerative disease worldwide. It is recognized clinically by severe complications in motor function caused by progressive degeneration of dopaminergic neurons (DAn) and dopamine depletion. As the current standard of treatment is focused on alleviating symptoms through Levodopa, developing neuroprotective techniques is critical for adopting a more pathology-oriented therapeutic approach. Regenerative cell therapy has provided us with an unrivalled platform for evaluating potentially effective novel methods for treating neurodegenerative illnesses over the last two decades. Mesenchymal stem cells (MSCs) are most promising, as they can differentiate into dopaminergic neurons and produce neurotrophic substances. The precise process by which stem cells repair neuronal injury is unknown, and MSC-derived exosomes are suggested to be responsible for a significant portion of such effects. The present review discusses the application of mesenchymal stem cells and MSC-derived exosomes in PD treatment.
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Affiliation(s)
| | - Milad Shirvaliloo
- Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Ali Hazrati
- Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Ali Shariati
- Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Farhad Jadidi Niaragh
- Department of Immunology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hamed Valizadeh
- Tuberculosis and Lung Disease Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Ahmadi
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. .,Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
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13
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Mesenchymal stem cells: A living carrier for active tumor-targeted delivery. Adv Drug Deliv Rev 2022; 185:114300. [PMID: 35447165 DOI: 10.1016/j.addr.2022.114300] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 03/22/2022] [Accepted: 04/12/2022] [Indexed: 12/16/2022]
Abstract
The strategy of using mesenchymal stem cells (MSCs) as a living carrier for active delivery of therapeutic agents targeting tumor sites has been attempted in a wide range of studies to validate the feasibility and efficacy for tumor treatment. This approach reveals powerful tumor targeting and tumor penetration. In addition, MSCs have been confirmed to actively participate in immunomodulation of the tumor microenvironment. Thus, MSCs are not inert delivery vehicles but have a strong impact on the fate of tumor cells. In this review, these active properties of MSCs are addressed to highlight the advantages and challenges of using MSCs for tumor-targeted delivery. In addition, some of the latest examples of using MSCs to carry a variety of anti-tumor agents for tumor-targeted therapy are summarized. Recent technologies to improve the performance and safety of this delivery strategy will be introduced. The advances, applications, and challenges summarized in this review will provide a general understanding of this promising strategy for actively delivering drugs to tumor tissues.
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14
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Stem cells therapy for thyroid diseases: progress and challenges. Curr Ther Res Clin Exp 2022; 96:100665. [PMID: 35371349 PMCID: PMC8968462 DOI: 10.1016/j.curtheres.2022.100665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2021] [Accepted: 02/25/2022] [Indexed: 11/18/2022] Open
Abstract
Background Thyroid hormones are indispensable for organ development and maintaining homeostasis. Thyroid diseases, including thyroiditis and thyroid cancer, affect the normal secretion of hormones and result in thyroid dysfunction. Objective This review focuses on therapeutic applications of stem cells for thyroid diseases. Methods A literature search of Medline and PubMed was conducted (January 2000–July 2021) to identify recent reports on stem cell therapy for thyroid diseases. Results Stem cells are partially developed cell types. They have the capacity to form specialized cells. Besides embryonic stem cells and mesenchymal stem cells, organ resident stem cells and cancer stem cells are recently reported to have important roles in forming organ specific cells and cancers. Stem cells, especially mesenchymal stem cells, have anti-inflammatory and anticancer functions as well. Conclusions This review outlines the therapeutic potency of embryonic stem cells, mesenchymal stem cells, thyroid resident stem cells, and thyroid cancer stem cells in thyroid cells’ regeneration, thyroid function modulation, thyroiditis suppression, and antithyroid cancers. Stem cells represent a promising form of treatment for thyroid disorders.
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15
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Huang T, Zhang T, Gao J. Targeted mitochondrial delivery: A therapeutic new era for disease treatment. J Control Release 2022; 343:89-106. [DOI: 10.1016/j.jconrel.2022.01.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Revised: 01/17/2022] [Accepted: 01/18/2022] [Indexed: 12/13/2022]
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16
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Melim C, Magalhães M, Santos AC, Campos EJ, Cabral C. Nanoparticles as phytochemical carriers for cancer treatment: News of the last decade. Expert Opin Drug Deliv 2022; 19:179-197. [PMID: 35166619 DOI: 10.1080/17425247.2022.2041599] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION The development and application of novel therapeutic medicines for the treatment of cancer are of vital importance to improve the disease's outcome and survival rate. One noteworthy treatment approach is the use of biologically active compounds present in natural products. Even though these phytocompounds present anti-inflammatory, antioxidant, and anticancer properties, their use is limited essentially due to poor systemic delivery, low bioavailability, and water solubility concerns. To make full use of the anticancer potential of natural products, these limitations need to be technologically addressed. In this sense, nanotechnology emerges as a promising drug delivery system strategy. AREAS COVERED In this review, the benefits and potential of nanodelivery systems for natural products encapsulation as promising therapeutic approaches for cancer, which were developed during the last decade, are highlighted. EXPERT OPINION The nanotechnology area has been under extensive research in the medical field given its capacity for improving the therapeutic potential of drugs by increasing their bioavailability and allowing a targeted delivery to the tumor site. Thereby, the nanoencapsulation of phytocompounds can have a direct impact on the recognized therapeutic activity of natural products towards cancer.
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Affiliation(s)
- Catarina Melim
- CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.,University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, 3000-548 Coimbra, Portugal.,University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal
| | - Mariana Magalhães
- CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.,University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, 3000-548 Coimbra, Portugal.,University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.,PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Casa Costa Alemão, 3030-789 Coimbra, Portugal
| | - Ana Cláudia Santos
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Polo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.,REQUIMTE/LAQV, Group of Pharmaceutical Technology, Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal
| | - Elisa Julião Campos
- University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, 3000-548 Coimbra, Portugal.,University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.,Association for Innovation and Biomedical Research on Light and Image (AIBILI), 3000-548 Coimbra, Portugal
| | - Célia Cabral
- University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Clinic Academic Center of Coimbra (CACC), Faculty of Medicine, 3000-548 Coimbra, Portugal.,University of Coimbra, Center for Innovative Biomedicine and Biotechnology (CIBB), 3000-548 Coimbra, Portugal.,Centre for Functional Ecology, Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal
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17
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Vicinanza C, Lombardi E, Da Ros F, Marangon M, Durante C, Mazzucato M, Agostini F. Modified mesenchymal stem cells in cancer therapy: A smart weapon requiring upgrades for wider clinical applications. World J Stem Cells 2022; 14:54-75. [PMID: 35126828 PMCID: PMC8788179 DOI: 10.4252/wjsc.v14.i1.54] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Revised: 08/06/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem stromal cells (MSC) are characterized by the intriguing capacity to home toward cancer cells after systemic administration. Thus, MSC can be harnessed as targeted delivery vehicles of cytotoxic agents against tumors. In cancer patients, MSC based advanced cellular therapies were shown to be safe but their clinical efficacy was limited. Indeed, the amount of systemically infused MSC actually homing to human cancer masses is insufficient to reduce tumor growth. Moreover, induction of an unequivocal anticancer cytotoxic phenotype in expanded MSC is necessary to achieve significant therapeutic efficacy. Ex vivo cell modifications are, thus, required to improve anti-cancer properties of MSC. MSC based cellular therapy products must be handled in compliance with good manufacturing practice (GMP) guidelines. In the present review we include MSC-improving manipulation approaches that, even though actually tested at preclinical level, could be compatible with GMP guidelines. In particular, we describe possible approaches to improve MSC homing on cancer, including genetic engineering, membrane modification and cytokine priming. Similarly, we discuss appropriate modalities aimed at inducing a marked cytotoxic phenotype in expanded MSC by direct chemotherapeutic drug loading or by genetic methods. In conclusion, we suggest that, to configure MSC as a powerful weapon against cancer, combinations of clinical grade compatible modification protocols that are currently selected, should be introduced in the final product. Highly standardized cancer clinical trials are required to test the efficacy of ameliorated MSC based cell therapies.
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Affiliation(s)
- Carla Vicinanza
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Elisabetta Lombardi
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Francesco Da Ros
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Miriam Marangon
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Cristina Durante
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Mario Mazzucato
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
| | - Francesco Agostini
- Stem Cell Unit, Centro di Riferimento Oncologico di Aviano, IRCCS, Aviano 33081, Italy
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18
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Xu D, Su Y, Xu Q, Huang T, Chen Z, Zhang T. Uniform iron oxide nanoparticles reduce the required amount of polyethylenimine in the gene delivery to mesenchymal stem cells. NANOTECHNOLOGY 2021; 33:125101. [PMID: 34874301 DOI: 10.1088/1361-6528/ac4066] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 12/06/2021] [Indexed: 06/13/2023]
Abstract
Cationic polyethylenimine (PEI) is regarded as the 'golden standard' of non-viral gene vectors. However, the superiority of PEI with high positive charge density also induces its major drawback of cytotoxicity, which restricts its application for an effective and safe gene delivery to stem cells. To redress this shortcoming, herein, a magnetic gene complex containing uniform iron oxide nanoparticles (UIONPs), plasmid DNA, and free PEI is prepared through electrostatic interactions for the gene delivery to bone marrow-derived mesenchymal stem cells (BM-MSCs). Results show that UIONPs dramatically promote the gene delivery to BM-MSCs using the assistance of magnetic force. In addition, decreasing the free PEI nitrogen to DNA phosphate (N/P) ratio from 10 to 6 has little adverse impact on the transgene expression levels (over 300 times than that of PEI alone at the N/P ratio of 6) and significantly reduces the cytotoxicity to BM-MSCs. Further investigations confirmed that the decrease of free PEI has little influence on the cellular uptake after applying external magnetic forces, but that the reduced positive charge density decreases the cytotoxicity. The present study demonstrates that magnetic gene delivery not only contributes to the enhanced gene expression but also helps to reduce the required amount of PEI, providing a potential strategy for an efficient and safe gene delivery to stem cells.
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Affiliation(s)
- Donghang Xu
- Department of Pharmacy, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Yuanqin Su
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China
| | - Qianhao Xu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China
| | - Ting Huang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China
| | - Zhilan Chen
- Department of Pharmacy, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China
| | - Tianyuan Zhang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China
- Dr Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, People's Republic of China
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19
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Sun G, Sun K, Sun J. Combination prostate cancer therapy: Prostate-specific membranes antigen targeted, pH-sensitive nanoparticles loaded with doxorubicin and tanshinone. Drug Deliv 2021; 28:1132-1140. [PMID: 34121558 PMCID: PMC8205064 DOI: 10.1080/10717544.2021.1931559] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Revised: 05/09/2021] [Accepted: 05/10/2021] [Indexed: 12/12/2022] Open
Abstract
Prostate cancer is the second most frequently diagnosed cancer in the men population. Combination anticancer therapy using doxorubicin (DOX) and another extract of traditional Chinese medicine is one nano-sized drug delivery system promising to generate synergistic anticancer effects, maximize the treatment effect, and overcome multi-drug resistance. The purpose of this study is to construct a drug delivery system for the co-delivery of DOX and tanshinones (TAN). Lipid nanoparticles loaded with DOX and TAN (N-DOX/TAN) were prepared by emulsification and solvent-diffusion method. PSMA targeted nanoparticles loaded with DOX and TAN (P-N-DOX/TAN) were synthesized by conjugating a PSMA targeted ligand to N-DOX/TAN. We evaluate the performance of this system in vitro and in vivo. P-N-DOX/TAN has a size of 139.7 ± 4.1 nm and a zeta potential of 11.2 ± 1.6 mV. The drug release of DOX and TAN from P-N-DOX/TAN was much faster than that of N-DOX/TAN. N-DOX/TAN presented more inhibition effect on tumor growth than N-DOX and N-TAN, which is consistent with the synergistic results and successfully highlighting the advantages of combing the DOX and TAN in one system. P-N-DOX/TAN achieved higher uptake by LNCaP cells (58.9 ± 1.9%), highest tumor tissue distribution, and the most significant tumor inhibition efficiency. The novel nanomedicine offers great promise for the dual drug delivery to prostate cancer cells, showing the potential of synergistic combination therapy for prostate cancer.
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Affiliation(s)
- Guanxing Sun
- Department of Oncology, Municipal Hospital of Zaozhuang, Zaozhuang, P. R. China
| | - Kai Sun
- Department of Pharmacy, Municipal Hospital of Zaozhuang, Zaozhuang, P. R. China
| | - Jie Sun
- Department of Pharmacy, Municipal Hospital of Zaozhuang, Zaozhuang, P. R. China
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20
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Huang T, Zhang T, Jiang X, Li A, Su Y, Bian Q, Wu H, Lin R, Li N, Cao H, Ling D, Wang J, Tabata Y, Gu Z, Gao J. Iron oxide nanoparticles augment the intercellular mitochondrial transfer-mediated therapy. SCIENCE ADVANCES 2021; 7:eabj0534. [PMID: 34586849 PMCID: PMC8480934 DOI: 10.1126/sciadv.abj0534] [Citation(s) in RCA: 72] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Accepted: 07/30/2021] [Indexed: 05/24/2023]
Abstract
The transfer of mitochondria between cells has recently been revealed as a spontaneous way to protect the injured cells. However, the utilization of this natural transfer process for disease treatment is so far limited by its unsatisfactory transfer efficiency and selectivity. Here, we demonstrate that iron oxide nanoparticles (IONPs) can augment the intercellular mitochondrial transfer from human mesenchymal stem cells (hMSCs) selectively to diseased cells, owing to the enhanced formation of connexin 43–containing gap junctional channels triggered by ionized IONPs. In a mouse model of pulmonary fibrosis, the IONP-engineered hMSCs achieve a remarkable mitigation of fibrotic progression because of the promoted intercellular mitochondrial transfer, with no serious safety issues identified. The present study reports a potential method of using IONPs to enable hMSCs for efficient and safe transfer of mitochondria to diseased cells to restore mitochondrial bioenergetics.
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Affiliation(s)
- Ting Huang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Tianyuan Zhang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China
| | - Xinchi Jiang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China
| | - Ai Li
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Yuanqin Su
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Qiong Bian
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Honghui Wu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Ruyi Lin
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Ni Li
- Department of Cardiothoracic Surgery, Ningbo Medical Center, Lihuili Hospital Affiliated to Ningbo University, Ningbo, Zhejiang 315041, China
| | - Hongcui Cao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Daishun Ling
- School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Jinqiang Wang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Yasuhiko Tabata
- Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
| | - Zhen Gu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jianqing Gao
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China
- Westlake Laboratory of Life Sciences and Biomedicine, Zhejiang, China
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21
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Li A, Zhang T, Huang T, Lin R, Mu J, Su Y, Sun H, Jiang X, Wu H, Xu D, Cao H, Sun X, Ling D, Gao J. Iron Oxide Nanoparticles Promote Cx43-Overexpression of Mesenchymal Stem Cells for Efficient Suicide Gene Therapy during Glioma Treatment. Theranostics 2021; 11:8254-8269. [PMID: 34373740 PMCID: PMC8344020 DOI: 10.7150/thno.60160] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Accepted: 06/21/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Mesenchymal stem cells (MSCs) have been applied as a promising vehicle for tumour-targeted delivery of suicide genes in the herpes simplex virus thymidine kinase (HSV-tk)/ganciclovir (GCV) suicide gene therapy against malignant gliomas. The efficiency of this strategy is largely dependent on the bystander effect, which relies on high suicide gene expression levels and efficient transportation of activated GCV towards glioma cells. However, up to now, the methods to enhance the bystander effect of this strategy in an efficient and safe way are still lacking and new approaches to improve this therapeutic strategy are required. Methods: In this study, MSCs were gene transfected using magnetosome-like ferrimagnetic iron oxide nanochains (MFIONs) to highly express HSV-tk. Both the suicide and bystander effects of HSV-tk expressed MSCs (MSCs-tk) were quantitatively evaluated. Connexin 43 (Cx43) expression by MSCs and glioma cells was measured under different treatments. Intercellular communication between MSCs and C6 glioma cells was examined using a dye transfer assay. Glioma tropism and the bio-distribution of MSCs-tk were observed. Anti-tumour activity was investigated in the orthotopic glioma of rats after intravenous administration of MSCs-tk followed by intraperitoneal injection of GCV. Results: Gene transfection using MFIONs achieved sufficient expression of HSV-tk and triggered Cx43 overexpression in MSCs. These Cx43 overexpressing MSCs promoted gap junction intercellular communication (GJIC) between MSCs and glioma cells, resulting in significantly inhibited growth of glioma through an improved bystander effect. Outstanding tumour targeting and significantly prolonged survival with decreased tumour size were observed after the treatment using MFION-transfected MSCs in glioma model rats. Conclusion: Our results show that iron oxide nanoparticles have the potential to improve the suicide gene expression levels of transfected MSCs, while promoting the GJIC formation between MSCs and tumour cells, which enhances the sensitivity of glioma cells to HSV-tk/GCV suicide gene therapy.
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Affiliation(s)
- Ai Li
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Tianyuan Zhang
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Cancer Center, Zhejiang University School of Medicine, Hangzhou, 310006, China
| | - Ting Huang
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Ruyi Lin
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jiafu Mu
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Yuanqin Su
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Hao Sun
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Xinchi Jiang
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China
| | - Honghui Wu
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Donghang Xu
- Department of Pharmacy, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
| | - Hongcui Cao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
| | - Xiaoyi Sun
- Department of Pharmacy, Zhejiang University City College, Hangzhou 310015, China
| | - Daishun Ling
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Jianqing Gao
- Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, China
- Cancer Center, Zhejiang University, Hangzhou, 310058, China
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22
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Ding Y, Wang C, Sun Z, Wu Y, You W, Mao Z, Wang W. Mesenchymal Stem Cells Engineered by Nonviral Vectors: A Powerful Tool in Cancer Gene Therapy. Pharmaceutics 2021; 13:pharmaceutics13060913. [PMID: 34205513 PMCID: PMC8235299 DOI: 10.3390/pharmaceutics13060913] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 06/09/2021] [Accepted: 06/16/2021] [Indexed: 12/14/2022] Open
Abstract
Due to their "tumor homing" and "immune privilege" characteristics, the use of mesenchymal stem cells (MSCs) has been proposed as a novel tool against cancer. MSCs are genetically engineered in vitro and then utilized to deliver tumoricidal agents, including prodrugs and bioactive molecules, to tumors. The genetic modification of MSCs can be achieved by various vectors, and in most cases viral vectors are used; however, viruses may be associated with carcinogenesis and immunogenicity, restricting their clinical translational potential. As such, nonviral vectors have emerged as a potential solution to address these limitations and have gradually attracted increasing attention. In this review, we briefly revisit the current knowledge about MSC-based cancer gene therapy. Then, we summarize the advantages and challenges of nonviral vectors for MSC transfection. Finally, we discuss recent advances in the development of new nonviral vectors, which have provided promising strategies to overcome obstacles in the gene modulation of MSCs.
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Affiliation(s)
- Yuan Ding
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; (Y.D.); (C.W.); (Z.S.); (Y.W.); (W.Y.)
- Key Laboratory, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China
- Research Center, Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, China
- Clinical Medicine Innovation Center, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease, Zhejiang University, Hangzhou 310009, China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, China
- Cancer Center, Zhejiang University, Hangzhou 310009, China
| | - Chenyang Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; (Y.D.); (C.W.); (Z.S.); (Y.W.); (W.Y.)
- Key Laboratory, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China
- Research Center, Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, China
- Clinical Medicine Innovation Center, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease, Zhejiang University, Hangzhou 310009, China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, China
- Cancer Center, Zhejiang University, Hangzhou 310009, China
| | - Zhongquan Sun
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; (Y.D.); (C.W.); (Z.S.); (Y.W.); (W.Y.)
- Key Laboratory, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China
- Research Center, Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, China
- Clinical Medicine Innovation Center, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease, Zhejiang University, Hangzhou 310009, China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, China
- Cancer Center, Zhejiang University, Hangzhou 310009, China
| | - Yingsheng Wu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; (Y.D.); (C.W.); (Z.S.); (Y.W.); (W.Y.)
- Key Laboratory, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China
- Research Center, Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, China
- Clinical Medicine Innovation Center, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease, Zhejiang University, Hangzhou 310009, China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, China
- Cancer Center, Zhejiang University, Hangzhou 310009, China
| | - Wanlu You
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; (Y.D.); (C.W.); (Z.S.); (Y.W.); (W.Y.)
- Key Laboratory, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China
- Research Center, Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, China
- Clinical Medicine Innovation Center, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease, Zhejiang University, Hangzhou 310009, China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, China
- Cancer Center, Zhejiang University, Hangzhou 310009, China
| | - Zhengwei Mao
- Key Laboratory, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China
- MOE Key Laboratory, Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China
- Correspondence: (Z.M.); (W.W.); Tel.: +86-15168215834 (Z.M.); +86-0571-87783820 (W.W.)
| | - Weilin Wang
- Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; (Y.D.); (C.W.); (Z.S.); (Y.W.); (W.Y.)
- Key Laboratory, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, Hangzhou 310009, China
- Research Center, Diagnosis and Treatment Technology for Hepatocellular Carcinoma of Zhejiang Province, Hangzhou 310009, China
- Clinical Medicine Innovation Center, Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Disease, Zhejiang University, Hangzhou 310009, China
- Clinical Research Center of Hepatobiliary and Pancreatic Diseases of Zhejiang Province, Hangzhou 310009, China
- Cancer Center, Zhejiang University, Hangzhou 310009, China
- Correspondence: (Z.M.); (W.W.); Tel.: +86-15168215834 (Z.M.); +86-0571-87783820 (W.W.)
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Attia N, Mashal M, Puras G, Pedraz JL. Mesenchymal Stem Cells as a Gene Delivery Tool: Promise, Problems, and Prospects. Pharmaceutics 2021; 13:843. [PMID: 34200425 PMCID: PMC8229096 DOI: 10.3390/pharmaceutics13060843] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/24/2021] [Accepted: 05/31/2021] [Indexed: 12/13/2022] Open
Abstract
The cell-based approach in gene therapy arises as a promising strategy to provide safe, targeted, and efficient gene delivery. Owing to their unique features, as homing and tumor-tropism, mesenchymal stem cells (MSCs) have recently been introduced as an encouraging vehicle in gene therapy. Nevertheless, non-viral transfer of nucleic acids into MSCs remains limited due to various factors related to the main stakeholders of the process (e.g., nucleic acids, carriers, or cells). In this review, we have summarized the main types of nucleic acids used to transfect MSCs, the pros and cons, and applications of each. Then, we have emphasized on the most efficient lipid-based carriers for nucleic acids to MSCs, their main features, and some of their applications. While a myriad of studies have demonstrated the therapeutic potential for engineered MSCs therapy in various illnesses, optimization for clinical use is an ongoing challenge. On the way of improvement, genetically modified MSCs have been combined with various novel techniques and tools (e.g., exosomes, spheroids, 3D-Bioprinting, etc.,) aiming for more efficient and safe applications in biomedicine.
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Affiliation(s)
- Noha Attia
- Laboratory of Pharmaceutics, NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; (N.A.); (M.M.)
- Department of Basic Sciences, The American University of Antigua-College of Medicine, Coolidge 1451, Antigua and Barbuda
- The Center of Research and Evaluation, The American University of Antigua-College of Medicine, Coolidge 1451, Antigua and Barbuda
- Histology and Cell Biology Department, Faculty of Medicine, University of Alexandria, Alexandria 21561, Egypt
| | - Mohamed Mashal
- Laboratory of Pharmaceutics, NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; (N.A.); (M.M.)
- The Center of Research and Evaluation, The American University of Antigua-College of Medicine, Coolidge 1451, Antigua and Barbuda
| | - Gustavo Puras
- Laboratory of Pharmaceutics, NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; (N.A.); (M.M.)
- Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, 28029 Madrid, Spain
- Bioaraba, NanoBioCel Research Group, 01006 Vitoria-Gasteiz, Spain
- Laboratory of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain
| | - Jose Luis Pedraz
- Laboratory of Pharmaceutics, NanoBioCel Research Group, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; (N.A.); (M.M.)
- Networking Research Centre of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Institute of Health Carlos III, 28029 Madrid, Spain
- Bioaraba, NanoBioCel Research Group, 01006 Vitoria-Gasteiz, Spain
- Laboratory of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain
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Li YS, Wu HH, Jiang XC, Zhang TY, Zhou Y, Huang LL, Zhi P, Tabata Y, Gao JQ. Active stealth and self-positioning biomimetic vehicles achieved effective antitumor therapy. J Control Release 2021; 335:515-526. [PMID: 34058269 DOI: 10.1016/j.jconrel.2021.05.031] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 04/15/2021] [Accepted: 05/22/2021] [Indexed: 01/27/2023]
Abstract
Mesenchymal stem cells (MSCs) are recognized as promising drug delivery vehicles. However, the limitation of drug loading capacity and safety considerations are two obstacles to the further application of MSCs. Here, we report MSC membrane-coated mesoporous silica nanoparticles (MSN@M) that maintain the active stealth and self-positioning drug delivery abilities of MSCs and resolve issues related to MSCs-mediated drug delivery. MSN@M was established through uniformly integrating MSC membrane onto a mesoporous silica nanoparticle (MSN) core by sonication. Reduced clearance of phagocytes mediated by CD47 marker on MSC membrane was observed in vitro, which explained the only ~ 25% clearance rate of MSN@M compared with MSN in vivo within 24 h. MSN@M also showed stronger tumor targeting and penetration ability compared with MSN in HepG2 tumor bearing mice. Simultaneously, MSN@M exhibited strong capacity for drug loading and sustained drug release ability of MSN when loaded with doxorubicin (DOX), the drug loading of MSN@M increased ~ 5 folds compared with MSC membrane. In HepG2 xenograft mice, DOX-loaded MSN@M effectively inhibited the growth of tumors and decreased the side effects of treatment by decreasing the exposure of other tissues to DOX. Consequently, our MSN@M may serve as alternative vehicles for MSCs and provide more options for antitumor treatment.
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Affiliation(s)
- Yao-Sheng Li
- Institute of Pharmaceutics, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China
| | - Hong-Hui Wu
- Institute of Pharmaceutics, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China
| | - Xin-Chi Jiang
- Institute of Pharmaceutics, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, PR China
| | - Tian-Yuan Zhang
- Institute of Pharmaceutics, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, PR China
| | - Yi Zhou
- Institute of Pharmaceutics, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China
| | - Ling-Ling Huang
- Institute of Pharmaceutics, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China
| | - Pei Zhi
- Institute of Pharmaceutics, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China
| | - Yasuhiko Tabata
- Laboratory of Biomaterials, Department of Regeneration Science and Engineering, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
| | - Jian-Qing Gao
- Institute of Pharmaceutics, Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou 310058, PR China; Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China; Cancer Center of Zhejiang University, Hangzhou 310058, PR China.
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25
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Wu J, Xie S, Li H, Zhang Y, Yue J, Yan C, Liu K, Liu Y, Xu R, Zheng G. Antitumor effect of IL-12 gene-modified bone marrow mesenchymal stem cells combined with Fuzheng Yiliu decoction in an in vivo glioma nude mouse model. J Transl Med 2021; 19:143. [PMID: 33827606 PMCID: PMC8028710 DOI: 10.1186/s12967-021-02809-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Accepted: 03/26/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Glioma is a complex cancer with a high morbidity and high mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown promise as an excellent cell/drug delivery vehicle for gene-targeted therapy; however, maintaining genetic stability and biological activity remains difficult. Furthermore, whether BMSCs support or inhibit tumor growth remains debated. This study investigated whether a traditional Chinese medicine fomular, Fuzheng Yiliu decoction (FYD) had a synergistic antitumor effect with IL-12 gene-modified BMSCs in glioma-bearing nude mice METHODS: The lentivirus-mediated IL-12 gene was transfected into primarily cultured BMSCs. A total of 72 BALB/c nude mice were used to establish xenograft models with glioma U251 cells and were divided into groups (n = 12) including blank control group, nude mouse model group (model group), lentiviral transfection of BMSC group with no gene loading (BMSC group), IL-12 lentivirus-transfected BMSC group (IL-12 + BMSC group), FYD treatment group (FYD group), and FYD treatment in IL-12 lentivirus-transfected BMSC group (FYD + IL-12 + BMSC group).. After treatment for 14 days, all mice were sacrificed to collect tumor tissue and serum for more detection, such as distribution of BMSCs, cell apoptosis in xenograft tumors, serum IL-12 and INF-γ levels, mouse weight and tumor volume were measured RESULTS: There were significantly more apoptotic cells in tumor tissue in IL-12 gene transfected group, FYD treatment group and FYD combining with IL-12 gene transfected group than that in the model group (P < 0.05). The FYD + IL-12 + BMSC group showed significantly higher Bax and lower Bcl-2 expression (P < 0.05), and serum IL-12 and INF-γ levels (P < 0.05) were higher than that in all other groups. After the intervention, this group also showed a strong inhibitory effect against tumor growth (P < 0.05) CONCLUSIONS: This study suggested FYD treatment combined with IL-12 gene-modified BMSCs shows synergistic antitumor effect in glioma-bearing nude mice.
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Affiliation(s)
- Jianjun Wu
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
- Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level, Lanzhou, 730000, Gansu, China
- Provincial Key Laboratory of Chinese Medicine Prevention and Control of Chronic Diseases, Lanzhou, 730000, Gansu, China
| | - Shoupin Xie
- Department of Neurology, The First People's Hospital of Lanzhou City, Lanzhou, 730050, China
| | - Hailong Li
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
- Provincial Key Laboratory of Chinese Medicine Prevention and Control of Chronic Diseases, Lanzhou, 730000, Gansu, China
| | - Yanxia Zhang
- Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level, Lanzhou, 730000, Gansu, China
- Provincial Key Laboratory of Chinese Medicine Prevention and Control of Chronic Diseases, Lanzhou, 730000, Gansu, China
| | - Jia Yue
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
- Provincial Key Laboratory of Chinese Medicine Prevention and Control of Chronic Diseases, Lanzhou, 730000, Gansu, China
| | - Chunlu Yan
- Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level, Lanzhou, 730000, Gansu, China
- School of Integrated Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Kai Liu
- Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level, Lanzhou, 730000, Gansu, China
- School of Integrated Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Yongqi Liu
- Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level, Lanzhou, 730000, Gansu, China
- School of Basic Medicine, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
| | - Rui Xu
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China
- Key Laboratory of Dunhuang Medicine and Transformation at Provincial and Ministerial Level, Lanzhou, 730000, Gansu, China
| | - Guisen Zheng
- School of Public Health, Gansu University of Chinese Medicine, Lanzhou, 730000, Gansu, China.
- Provincial Key Laboratory of Chinese Medicine Prevention and Control of Chronic Diseases, Lanzhou, 730000, Gansu, China.
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Zhang T, Huang T, Su Y, Gao J. Mesenchymal Stem Cells‐Based Targeting Delivery System: Therapeutic Promises and Immunomodulation against Tumor. ADVANCED THERAPEUTICS 2021. [DOI: 10.1002/adtp.202100030] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- Tianyuan Zhang
- Zhejiang Province Key Laboratory of Anti‐Cancer Drug Research College of Pharmaceutical Sciences Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
| | - Ting Huang
- Zhejiang Province Key Laboratory of Anti‐Cancer Drug Research College of Pharmaceutical Sciences Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
| | - Yuanqin Su
- Zhejiang Province Key Laboratory of Anti‐Cancer Drug Research College of Pharmaceutical Sciences Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
| | - Jianqing Gao
- Zhejiang Province Key Laboratory of Anti‐Cancer Drug Research College of Pharmaceutical Sciences Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
- Cancer Center of Zhejiang University 866 Yuhangtang Rd Hangzhou 310058 China
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Das MK, Lunavat TR, Miletic H, Hossain JA. The Potentials and Pitfalls of Using Adult Stem Cells in Cancer Treatment. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1326:139-157. [PMID: 33615422 DOI: 10.1007/5584_2021_619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Stem cells play a pivotal role in the developmental stages of an organism and in adulthood as well. Therefore, it is not surprising that stem cells constitute a focus of extensive research. Indeed, several decades of stem cell research have tremendously increased our knowledge on the mechanistic understandings of stem cell biology. Interestingly, revealing the fundamental principles of stem cell biology has also fostered its application for therapeutic purposes. Many of the attributes that the stem cells possess, some of which are unique, allow multifaceted exploitation of stem cells in the treatment of various diseases. Cancer, the leading cause of mortality worldwide, is one of the disease groups that has been benefited by the potentials of therapeutic applications of the stem cells. While the modi operandi of how stem cells contribute to cancer treatment are many-sided, two major principles can be conceived. One mode involves harnessing the regenerative power of the stem cells to promote the generation of blood-forming cells in cancer patients after cytotoxic regimens. A totally different kind of utility of stem cells has been exercised in another mode where the stem cells can potentially deliver a plethora of anti-cancer therapeutics in a tumor-specific manner. While both these approaches can improve the treatment of cancer patients, there exist several issues that warrant further research. This review summarizes the basic principles of the utility of the stem cells in cancer treatment along with the current trends and pinpoints the major obstacles to focus on in the future for further improvement.
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Affiliation(s)
- Mrinal K Das
- Department of Molecular Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
| | - Taral R Lunavat
- Department of Biomedicine, University of Bergen, Bergen, Norway
| | - Hrvoje Miletic
- Department of Biomedicine, University of Bergen, Bergen, Norway.,Department of Pathology, Haukeland University Hospital, Bergen, Norway
| | - Jubayer A Hossain
- Department of Biomedicine, University of Bergen, Bergen, Norway. .,Department of Pathology, Haukeland University Hospital, Bergen, Norway.
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Raychaudhuri R, Naik S, Shreya AB, Kandpal N, Pandey A, Kalthur G, Mutalik S. Pullulan based stimuli responsive and sub cellular targeted nanoplatforms for biomedical application: Synthesis, nanoformulations and toxicological perspective. Int J Biol Macromol 2020; 161:1189-1205. [PMID: 32504712 DOI: 10.1016/j.ijbiomac.2020.05.262] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 05/23/2020] [Accepted: 05/29/2020] [Indexed: 01/27/2023]
Abstract
With growing interest in polymers of natural origin, innumerable polysaccharides have gained attention for their biomedical application. Pullulan, one of the FDA approved nutraceuticals, possesses multiple unique properties which make them highly advantageous for biomedical applications. This present review encompasses the sources, production, properties and applications of pullulan. It highlights various pullulan based stimuli-responsive systems (temperature, pH, ultrasound, magnetic), subcellular targeted systems (mitochondria, Golgi apparatus/endoplasmic reticulum, lysosome, endosome), lipid-vesicular systems (solid-lipid nanoparticles, liposomes), polymeric nanofibres, micelles, inorganic (SPIONs, gold and silver nanoparticles), carbon-based nanoplatforms (carbon nanotubes, fullerenes, nanodiamonds) and quantum dots. This article also gives insight into different biomedical, therapeutic and diagnostic applications of pullulan viz., imaging, tumor targeting, stem cell therapy, gene therapy, vaccine delivery, cosmetic applications, protein delivery, tissue engineering, photodynamic therapy and chaperone-like activities. The review also includes the toxicological profile of pullulan which is helpful for the development of suitable delivery systems for clinical applications.
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Affiliation(s)
- Ruchira Raychaudhuri
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka State, India
| | - Santoshi Naik
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka State, India
| | - Ajjappla B Shreya
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka State, India
| | - Neha Kandpal
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka State, India
| | - Abhijeet Pandey
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka State, India
| | - Guruprasad Kalthur
- Department of Clinical Embryology, Kasturba Medical College, Manipal Academy of Higher Education, Manipal 576104, Karnataka State, India
| | - Srinivas Mutalik
- Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal 576104, Karnataka State, India.
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Zhang T, Xu Q, Huang T, Ling D, Gao J. New Insights into Biocompatible Iron Oxide Nanoparticles: A Potential Booster of Gene Delivery to Stem Cells. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2020; 16:e2001588. [PMID: 32725792 DOI: 10.1002/smll.202001588] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 05/10/2020] [Indexed: 06/11/2023]
Abstract
Gene delivery to stem cells is a critical issue of stem cells-based therapies, still facing ongoing challenges regarding efficiency and safety. Recent advances in the controlled synthesis of biocompatible magnetic iron oxide nanoparticles (IONPs) have provided a powerful nanotool for assisting gene delivery to stem cells. However, this field is still at an early stage, with well-designed and scalable IONPs synthesis highly desired. Furthermore, the potential risks or bioeffects of IONPs on stem cells are not completely figured out. Therefore, in this review, the updated researches focused on the gene delivery to stem cells using various designed IONPs are highlighted. Additionally, the impacts of the physicochemical properties of IONPs, as well as the magnetofection systems on the gene delivery performance and biocompatibility are summarized. Finally, challenges attributed to the potential impacts of IONPs on the biologic behaviors of stem cells and the large-scale productions of uniform IONPs are emphasized. The principles and challenges summarized in this review provide a general guidance for the rational design of IONPs-assisted gene delivery to stem cells.
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Affiliation(s)
- Tianyuan Zhang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, 310058, China
| | - Qianhao Xu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Ting Huang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Daishun Ling
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
| | - Jianqing Gao
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, 310058, China
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Levy O, Kuai R, Siren EMJ, Bhere D, Milton Y, Nissar N, De Biasio M, Heinelt M, Reeve B, Abdi R, Alturki M, Fallatah M, Almalik A, Alhasan AH, Shah K, Karp JM. Shattering barriers toward clinically meaningful MSC therapies. SCIENCE ADVANCES 2020; 6:eaba6884. [PMID: 32832666 PMCID: PMC7439491 DOI: 10.1126/sciadv.aba6884] [Citation(s) in RCA: 420] [Impact Index Per Article: 84.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 06/05/2020] [Indexed: 05/11/2023]
Abstract
More than 1050 clinical trials are registered at FDA.gov that explore multipotent mesenchymal stromal cells (MSCs) for nearly every clinical application imaginable, including neurodegenerative and cardiac disorders, perianal fistulas, graft-versus-host disease, COVID-19, and cancer. Several companies have or are in the process of commercializing MSC-based therapies. However, most of the clinical-stage MSC therapies have been unable to meet primary efficacy end points. The innate therapeutic functions of MSCs administered to humans are not as robust as demonstrated in preclinical studies, and in general, the translation of cell-based therapy is impaired by a myriad of steps that introduce heterogeneity. In this review, we discuss the major clinical challenges with MSC therapies, the details of these challenges, and the potential bioengineering approaches that leverage the unique biology of MSCs to overcome the challenges and achieve more potent and versatile therapies.
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Affiliation(s)
- Oren Levy
- Center for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Boston, MA, USA
| | - Rui Kuai
- Center for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Boston, MA, USA
- BWH Center of Excellence for Biomedicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Erika M. J. Siren
- Center for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Boston, MA, USA
| | - Deepak Bhere
- BWH Center of Excellence for Biomedicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Center for Stem Cell Therapeutics and Imaging, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Yuka Milton
- Center for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Boston, MA, USA
| | - Nabeel Nissar
- Center for Stem Cell Therapeutics and Imaging, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Michael De Biasio
- Center for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Boston, MA, USA
| | - Martina Heinelt
- Center for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Boston, MA, USA
| | - Brock Reeve
- Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA
| | - Reza Abdi
- Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - Meshael Alturki
- National Center of Pharmaceutical Technology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia
- KACST Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia
| | - Mohanad Fallatah
- KACST Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia
| | - Abdulaziz Almalik
- National Center of Pharmaceutical Technology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia
- KACST Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia
| | - Ali H. Alhasan
- National Center of Pharmaceutical Technology, Life Science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia
- KACST Center of Excellence for Biomedicine, Joint Centers of Excellence Program, King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia
| | - Khalid Shah
- BWH Center of Excellence for Biomedicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Center for Stem Cell Therapeutics and Imaging, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA
| | - Jeffrey M. Karp
- Center for Nanomedicine and Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Harvard-MIT Division of Health Sciences and Technology, Boston, MA, USA
- BWH Center of Excellence for Biomedicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
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LI A, ZHANG T, GAO J. [Progress on utilizing mesenchymal stem cells as cellular delivery system for targeting delivery of as drug/gene for anti-tumor therapy]. Zhejiang Da Xue Xue Bao Yi Xue Ban 2020; 49:20-34. [PMID: 32621413 PMCID: PMC8800717 DOI: 10.3785/j.issn.1008-9292.2020.02.22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 01/15/2020] [Indexed: 06/11/2023]
Abstract
Mesenchymal stem cells (MSCs) have the inherent tumor-homing ability with the attraction of multiple chemokines released by tumor tissues or tumor microenvironments, which can be utilized as promising cellular carriers for targeted delivery of anti-tumor drugs and genes. In most circumstances, large amount of systemicly administrated MSCs will be firstly trapped by lungs, following with re-distribution and homing to tumor tissues after lung clearance. Several approaches like enhanced interactions between chemokines and receptors on MSCs or reducing the retention of MSCs by changes of administration methods are firstly reviewed for improving the homing of MSCs towards tumor tissues. Additionally, the potentials and gains of utilizing MSCs to carry several chemotherapeutics, such as doxorubicin, paclitaxel and gemcitabine are summarized, showing the advantages of overcoming the short half-life and poor tumor targeting of these chemotherapeutics. Moreover, the applications of MSCs to protect and deliver therapeutic genes to tumor sites for selectively tumor cells eliminating or promoting immune system are highlighted. In addition, the potentials of using MSCs for tumor-targeting delivery of diagnostic and therapeutic agents are addressed. We believed that the continuous improvement and optimization of this stem cells-based cellular delivery system will provide a novel delivery strategy and option for tumor treatment.
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Therapeutic Mesenchymal Stromal Cells for Immunotherapy and for Gene and Drug Delivery. MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT 2020; 16:204-224. [PMID: 32071924 PMCID: PMC7012781 DOI: 10.1016/j.omtm.2020.01.005] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Mesenchymal stromal cells (MSCs) possess several fairly unique properties that, when combined, make them ideally suited for cellular-based immunotherapy and as vehicles for gene and drug delivery for a wide range of diseases and disorders. Key among these are: (1) their relative ease of isolation from a variety of tissues; (2) the ability to be expanded in culture without a loss of functionality, a property that varies to some degree with tissue source; (3) they are relatively immune-inert, perhaps obviating the need for precise donor/recipient matching; (4) they possess potent immunomodulatory functions that can be tailored by so-called licensing in vitro and in vivo; (5) the efficiency with which they can be modified with viral-based vectors; and (6) their almost uncanny ability to selectively home to damaged tissues, tumors, and metastases following systemic administration. In this review, we summarize the latest research in the immunological properties of MSCs, their use as immunomodulatory/anti-inflammatory agents, methods for licensing MSCs to customize their immunological profile, and their use as vehicles for transferring both therapeutic genes in genetic disease and drugs and genes designed to destroy tumor cells.
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Wu J, Wu H, Nakagawa S, Gao J. Virus-derived materials: bury the hatchet with old foes. Biomater Sci 2020; 8:1058-1072. [DOI: 10.1039/c9bm01383k] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Viruses, with special architecture and unique biological nature, can be utilized for various biomedical applications.
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Affiliation(s)
- Jiahe Wu
- Institute of Pharmaceutics
- College of Pharmaceutical Sciences
- Zhejiang University
- Hangzhou 310058
- China
| | - Honghui Wu
- Institute of Pharmaceutics
- College of Pharmaceutical Sciences
- Zhejiang University
- Hangzhou 310058
- China
| | - Shinsaku Nakagawa
- Department of Pharmaceutics
- Graduate School of Pharmaceutical Sciences
- Osaka University
- Suita
- Japan
| | - Jianqing Gao
- Institute of Pharmaceutics
- College of Pharmaceutical Sciences
- Zhejiang University
- Hangzhou 310058
- China
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Ouyang X, Wang X, Kraatz HB, Ahmadi S, Gao J, Lv Y, Sun X, Huang Y. A Trojan horse biomimetic delivery strategy using mesenchymal stem cells for PDT/PTT therapy against lung melanoma metastasis. Biomater Sci 2019; 8:1160-1170. [PMID: 31848537 DOI: 10.1039/c9bm01401b] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Mesenchymal stem cell (MSC)-based biomimetic delivery has been actively explored for drug accumulation and penetration into tumors by taking advantage of the tumor-tropic and penetration properties of MSCs. In this work, we further demonstrated the feasibility of MSC-mediated nano drug delivery, which was characterized by the "Trojan horse"-like transport via an endocytosis-exocytosis-endocytosis process between MSCs and cancer cells. Chlorin e6 (Ce6)-conjugated polydopamine nanoparticles (PDA-Ce6) were developed and loaded into the MSCs. Phototherapeutic agents are safe to the MSCs, and their very low dark toxicity causes no impairment of the inherent properties of MSCs, including tumor-homing ability. The MSCs loaded with PDA-Ce6 (MSC-PDA-Ce6) were able to target and penetrate into tumors and exocytose 60% of the payloads in 72 h. The released PDA-Ce6 NPs could penetrate deep and be re-endocytosed by the cancer cells. MSC-PDA-Ce6 tended to accumulate in the lungs and delivered PDA-Ce6 into the tumors after intravenous injection in the mouse model with lung melanoma metastasis. Phototoxicity can be selectively triggered in the tumors by sequentially treating with near-infrared irradiation to induce photodynamic therapy (PDT) and photothermal therapy (PTT). The MSC-based biomimetic delivery of PDA-Ce6 nanoparticles is a potential method for dual phototherapy against lung melanoma metastasis.
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Affiliation(s)
- Xumei Ouyang
- Department of Pharmacy, Zhejiang University City College, Hangzhou 310015, China. and Department of Pharmacy, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325035, China and Department of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Xiaoling Wang
- Department of Pharmacy, Zhejiang University City College, Hangzhou 310015, China. and Department of Pharmacy, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325035, China
| | - Heinz-Bernhard Kraatz
- Department of Physical and Environmental Sciences, University of Toronto Scarborough, Toronto, ON M1C 1A4, Canada
| | - Soha Ahmadi
- Department of Physical and Environmental Sciences, University of Toronto Scarborough, Toronto, ON M1C 1A4, Canada
| | - Jianqing Gao
- Department of Pharmacy, School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325035, China
| | - Yuanyuan Lv
- Department of Pharmacy, Zhejiang University City College, Hangzhou 310015, China.
| | - Xiaoyi Sun
- Department of Pharmacy, Zhejiang University City College, Hangzhou 310015, China.
| | - Yongzhuo Huang
- State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Rd, Shanghai, 201203, China.
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Xu M, Asghar S, Dai S, Wang Y, Feng S, Jin L, Shao F, Xiao Y. Mesenchymal stem cells-curcumin loaded chitosan nanoparticles hybrid vectors for tumor-tropic therapy. Int J Biol Macromol 2019; 134:1002-1012. [DOI: 10.1016/j.ijbiomac.2019.04.201] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Revised: 04/11/2019] [Accepted: 04/30/2019] [Indexed: 01/04/2023]
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Ceballos MP, Rigalli JP, Ceré LI, Semeniuk M, Catania VA, Ruiz ML. ABC Transporters: Regulation and Association with Multidrug Resistance in Hepatocellular Carcinoma and Colorectal Carcinoma. Curr Med Chem 2019; 26:1224-1250. [PMID: 29303075 DOI: 10.2174/0929867325666180105103637] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 10/19/2017] [Accepted: 11/21/2017] [Indexed: 02/07/2023]
Abstract
For most cancers, the treatment of choice is still chemotherapy despite its severe adverse effects, systemic toxicity and limited efficacy due to the development of multidrug resistance (MDR). MDR leads to chemotherapy failure generally associated with a decrease in drug concentration inside cancer cells, frequently due to the overexpression of ABC transporters such as P-glycoprotein (P-gp/MDR1/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs), and breast cancer resistance protein (BCRP/ABCG2), which limits the efficacy of chemotherapeutic drugs. The aim of this review is to compile information about transcriptional and post-transcriptional regulation of ABC transporters and discuss their role in mediating MDR in cancer cells. This review also focuses on drug resistance by ABC efflux transporters in cancer cells, particularly hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) cells. Some aspects of the chemotherapy failure and future directions to overcome this problem are also discussed.
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Affiliation(s)
- María Paula Ceballos
- Institute of Experimental Physiology, Faculty of Biochemical and Pharmaceutical Science, Rosario National University, Rosario, Argentina
| | - Juan Pablo Rigalli
- Institute of Experimental Physiology, Faculty of Biochemical and Pharmaceutical Science, Rosario National University, Rosario, Argentina.,Department of Clinical Pharmacology and Pharmacoepidemiology, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
| | - Lucila Inés Ceré
- Institute of Experimental Physiology, Faculty of Biochemical and Pharmaceutical Science, Rosario National University, Rosario, Argentina
| | - Mariana Semeniuk
- Institute of Experimental Physiology, Faculty of Biochemical and Pharmaceutical Science, Rosario National University, Rosario, Argentina
| | - Viviana Alicia Catania
- Institute of Experimental Physiology, Faculty of Biochemical and Pharmaceutical Science, Rosario National University, Rosario, Argentina
| | - María Laura Ruiz
- Institute of Experimental Physiology, Faculty of Biochemical and Pharmaceutical Science, Rosario National University, Rosario, Argentina
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Zhang T, Li F, Xu Q, Wang Q, Jiang X, Liang Z, Liao H, Kong X, Liu J, Wu H, Zhang D, An C, Dong L, Lu Y, Cao H, Kim D, Sun J, Hyeon T, Gao J, Ling D. Ferrimagnetic Nanochains‐Based Mesenchymal Stem Cell Engineering for Highly Efficient Post‐Stroke Recovery. ADVANCED FUNCTIONAL MATERIALS 2019; 29. [DOI: 10.1002/adfm.201900603] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/19/2019] [Indexed: 03/10/2025]
Abstract
AbstractUnsatisfactory post‐stroke recovery has long been a negative factor in the prognosis of ischemic stroke due to the lack of pharmacological treatments. Mesenchymal stem cells (MSCs)‐based therapy has recently emerged as a promising strategy redefining stroke treatment; however, its effectiveness has been largely restricted by insufficient therapeutic gene expression and inadequate cell numbers in the ischemic cerebrum. Herein, a non‐viral and magnetic field‐independent gene transfection approach is reported, using magnetosome‐like ferrimagnetic iron oxide nanochains (MFIONs), to genetically engineer MSCs for highly efficient post‐stroke recovery. The 1D MFIONs show efficient cellular uptake by MSCs, which results in highly efficient genetic engineering of MSCs to overexpress brain‐derived neurotrophic factor for treating ischemic cerebrum. Moreover, the internalized MFIONs promote the homing of MSCs to the ischemic cerebrum by upregulating CXCR4. Consequently, a pronounced recovery from ischemic stroke is achieved using MFION‐engineered MSCs in a mouse model.
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Affiliation(s)
- Tianyuan Zhang
- College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cell and Regenerative Medicine Zhejiang University Hangzhou 310058 China
| | - Fangyuan Li
- College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
| | - Qianhao Xu
- College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
| | - Qiyue Wang
- College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
| | - Xinchi Jiang
- College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
| | - Zeyu Liang
- College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
| | - Hongwei Liao
- College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
| | - Xianglei Kong
- Department of Radiology Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou 310016 China
| | - Jianan Liu
- Center for Nanoparticle Research Institute for Basic Science (IBS) Seoul 08826 Republic of Korea
- School of Chemical and Biological Engineering Seoul National University Seoul 08826 Republic of Korea
| | - Honghui Wu
- College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
| | - Danping Zhang
- College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
| | - Changhua An
- School of Chemistry and Chemical Engineering Tianjin University of Technology Tianjin 300384 China
| | - Liang Dong
- Division of Nanomaterials and Chemistry Hefei National Research Centre for Physical Sciences at the Microscale Department of Chemistry University of Science and Technology of China Hefei 230026 China
| | - Yang Lu
- School of Chemistry and Chemical Engineering Hefei University of Technology Hefei 230009 China
| | - Hongcui Cao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases the First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 China
| | - Dokyoon Kim
- Center for Nanoparticle Research Institute for Basic Science (IBS) Seoul 08826 Republic of Korea
- School of Chemical and Biological Engineering Seoul National University Seoul 08826 Republic of Korea
| | - Jihong Sun
- Department of Radiology Sir Run Run Shaw Hospital School of Medicine Zhejiang University Hangzhou 310016 China
| | - Taeghwan Hyeon
- Center for Nanoparticle Research Institute for Basic Science (IBS) Seoul 08826 Republic of Korea
- School of Chemical and Biological Engineering Seoul National University Seoul 08826 Republic of Korea
| | - Jianqing Gao
- College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
- Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cell and Regenerative Medicine Zhejiang University Hangzhou 310058 China
| | - Daishun Ling
- College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
- Key Laboratory of Biomedical Engineering of the Ministry of Education College of Biomedical Engineering & Instrument Science Zhejiang University Hangzhou 310027 China
- Hangzhou Institute of Innovative Medicine Zhejiang University Hangzhou 310012 China
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Wang Q, Zhong Y, Liu W, Wang Z, Gu L, Li X, Zheng J, Du H, Zhong Z, Xie F. Enhanced chemotherapeutic efficacy of the low-dose doxorubicin in breast cancer via nanoparticle delivery system crosslinked hyaluronic acid. Drug Deliv 2019; 26:12-22. [PMID: 30691317 PMCID: PMC6352940 DOI: 10.1080/10717544.2018.1507057] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Despite the development of treatment options in breast cancer, many patients die of recurrence and metastasis. Owing to enhanced permeability and retention in solid tumor tissue, nanoparticle (NP) delivery systems have been emerged as novel strategy in cancer chemotherapy. As extracellular matrix, glycosaminoglycan hyaluronan (HA) could bind its surface receptor adhesion molecule CD44 which is strongly expressed on breast cancer. We have previously reported a doxorubicin (DOX)-loaded HA-Lys-LA X-NPs (X-NP-DOX) NP delivery system for breast cancer treatment. In this study, we further investigated the antitumor effect of X-NP-DOX NP delivery system using low-dose DOX in both in vitro and in vivo systems. We demonstrated that low-dose X-NP-DOX possessed the ability for inhibiting MCF-7 breast cancer cell growth, invasion, and migration, and inducing apoptosis in vitro. In in vivo experiments, injection of low-dose X-NP-DOX into tumor-bearing mouse resulted in significant reduction of tumor size. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining further revealed that low-dose X-NP-DOX induced higher percentage of apoptotic cells compared with free DOX or saline. Furthermore, our study demonstrated that low-dose X-NP-DOX inhibited Notch1 and Ras/MAPK pathways, decreased cancer stem cell population, and reduced tumorigenesis compared to free DOX in both in vitro and in vivo settings. Owing to its enhanced efficacy and higher targetability compared to free DOX, low-dose DOX delivered by NP system may be a promising novel strategy for breast cancer treatment.
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Affiliation(s)
- Qin Wang
- a Department of Pathology, Institutes of Biology and Medical Sciences , Soochow University Medical College, Soochow University , Suzhou P. R. China.,b Department of Immunology, Institutes of Biology and Medical Sciences , Soochow University Medical College, Soochow University , Suzhou , P. R. China
| | - Yinan Zhong
- c Biomedical Polymers Laboratory, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science , Soochow University , Suzhou P. R. China
| | - Wenting Liu
- a Department of Pathology, Institutes of Biology and Medical Sciences , Soochow University Medical College, Soochow University , Suzhou P. R. China.,d Department of Pathology , The Frist Affiliated Hospital of Soochow University , Suzhou , P.R. China
| | - Zemin Wang
- e Investigative Toxicology and Pathology Laboratory, School of Public Health , Indiana University , Bloomington , IN , USA
| | - Liqin Gu
- f Department of Pathology , Taicang Traditional Medicine Hospital of Jiangsu Province , Taicang , P.R. China
| | - Xuejiao Li
- a Department of Pathology, Institutes of Biology and Medical Sciences , Soochow University Medical College, Soochow University , Suzhou P. R. China
| | - Jiqing Zheng
- a Department of Pathology, Institutes of Biology and Medical Sciences , Soochow University Medical College, Soochow University , Suzhou P. R. China
| | - Huan Du
- a Department of Pathology, Institutes of Biology and Medical Sciences , Soochow University Medical College, Soochow University , Suzhou P. R. China
| | - Zhiyuan Zhong
- c Biomedical Polymers Laboratory, Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials Science , Soochow University , Suzhou P. R. China
| | - Fang Xie
- a Department of Pathology, Institutes of Biology and Medical Sciences , Soochow University Medical College, Soochow University , Suzhou P. R. China
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Cheng XX, Yang QY, Qi YL, Liu ZZ, Liu D, He S, Yang LH, Xie J. Apoptosis of mesenchymal stem cells is regulated by Rspo1 via the Wnt/β-catenin signaling pathway. Chronic Dis Transl Med 2019; 5:53-63. [PMID: 30993264 PMCID: PMC6450805 DOI: 10.1016/j.cdtm.2019.02.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2018] [Indexed: 01/19/2023] Open
Abstract
Objective The aim of this study was to investigate the effect and possible mechanism of action of roof plate-specific spondin1 (Rspo1) in the apoptosis of rat bone marrow mesenchymal stem cells (BMSCs). Methods Osteogenic and adipogenic differentiation of BMSCs was identified by Alizarin Red and Oil Red O staining, respectively. BMSC surface markers (cluster of differentiation 29 [CD29], CD90, and CD45) were detected using flow cytometry. BMSCs were transfected with an adenoviral vector encoding Rspo1 (BMSCs-Rspo1 group). The expression levels of Rspo1 gene and Rspo1 protein in the BMSCs-Rspo1 group and the two control groups (untransfected BMSCs group and BMSCs-green fluorescent protein [GFP] group) were analyzed and compared by quantitative polymerase chain reaction and Western blot. The occurrence of apoptosis in the three groups was detected by flow cytometry and acridine orange-ethidium bromide (AO-EB) double dyeing. The activity of the Wnt/β-catenin signaling pathway was evaluated by measuring the expression levels of the key proteins of the pathway (β-catenin, c-Jun N-terminal kinase [JNK], and phospho-JNK). Results Osteogenic and adipogenic differentiation was confirmed in cultured BMSCs by the positive expression of CD29 and CD90 and the negative expression of CD45. Significantly increased expression levels of Rspo1 protein in the BMSCs-Rspo1 group compared to those in the BMSCs (0.60 ± 0.05 vs. 0.13 ± 0.02; t=95.007, P=0.001) and BMSCs-GFP groups (0.60 ± 0.05 vs. 0.10 ± 0.02; t=104.842, P=0.001) were observed. The apoptotic rate was significantly lower in the BMSCs-Rspo1 group compared with those in the BMSCs group ([24.06 ± 2.37]% vs. [40.87 ± 2.82]%; t = 49.872, P = 0.002) and the BMSCs-GFP group ([24.06 ± 2.37]% vs. [42.34 ± 0.26]%; t = 62.358, P = 0.001). In addition, compared to the BMSCs group, the protein expression levels of β-catenin (2.67 ± 0.19 vs. 1.14 ± 0.14; t = −9.217, P = 0.000) and JNK (1.87 ± 0.17 vs. 0.61 ± 0.07; t = −22.289, P = 0.000) were increased in the BMSCs-Rspo1 group. Compared to the BMSCs-GFP group, the protein expression levels of β-catenin (2.67 ± 0.19 vs. 1.44 ± 0.14; t = −5.692, P = 0.000) and JNK (1.87 ± 0.17 vs. 0.53 ± 0.06; t = −10.589, P = 0.000) were also upregulated in the BMSCs-Rspo1 group. Moreover, the protein expression levels of phospho-JNK were increased in the BMSCs-Rspo1 group compared to those in the BMSCs group (1.89 ± 0.10 vs. 0.63 ± 0.09; t = −8.975, P = 0.001) and the BMSCs-GFP group (1.89 ± 0.10 vs. 0.69 ± 0.08; t = −9.483, P = 0.001). Conclusion The Wnt/β-catenin pathway could play a vital role in the Rspo1-mediated inhibition of apoptosis in BMSCs.
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Affiliation(s)
- Xiao-Xia Cheng
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Qiao-Yan Yang
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China.,The First Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Yong-Li Qi
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China.,Huaihe Hospital of Henan University, Kaifeng, Henan 475000, China
| | - Zhi-Zhen Liu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Dan Liu
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Sheng He
- The First Affiliated Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Li-Hong Yang
- Department of Pathology, Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Jun Xie
- Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, Shanxi 030001, China
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Huang T, Li N, Gao J. Recent strategies on targeted delivery of thrombolytics. Asian J Pharm Sci 2019; 14:233-247. [PMID: 32104455 PMCID: PMC7032080 DOI: 10.1016/j.ajps.2018.12.004] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2018] [Revised: 12/12/2018] [Accepted: 12/26/2018] [Indexed: 12/18/2022] Open
Abstract
Thrombus formed in blood vessel is a progressive process, which would lead to life-threatening thrombotic diseases such as ischemic stroke. Unlike other diseases, the recognition of thrombus is usually in the late stage where blood vessels are largely blocked. So acute thrombotic diseases have a narrow therapeutic window, and remain leading causes of morbidity and mortality, whereas current thrombolysis therapy has limited therapeutic effects and bleeding complications. Thrombolytic agents in unwanted sites would cause hemorrhage due to the activation of plasminogen. Moreover, untargeted thrombolysis therapy require large amounts of thrombolytic agents, which in return would enhance hemorrhage risk. To improve the efficiency while minimizing the adverse effects of traditional thrombolysis therapy, novel drug delivery systems have been investigated. Various targeting strategies including ultrasound and magnetic field directed targeting, and specific binding, have been designed to deliver thrombolytic drugs to the thrombotic sites. These strategies demonstrate promising results in reducing bleeding risk as well as allowing less dosage of thrombolytic drugs with lowered clot lysis time. In this review, we discuss recent progress on targeted delivery of thrombolytics, and summarize treatment advantages and shortcomings, potentially helping to further promote the development of targeted thrombolysis.
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Affiliation(s)
- Ting Huang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Ni Li
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.,Department of Cardiothoracic Surgery, Ningbo Medical Centre Lihuili Hospital, Ningbo University, Ningbo 315041, China
| | - Jianqing Gao
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
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Monteiro BS, Santos BSD, Almeida BLD, Hiura E, Fiorio WAB, Valdetaro GP, Gonçalves DV, Silva CS, Champion T, Campagnol D. Adipose tissue derived mesenchymal stem cell transplantation in the treatment of ischemia/reperfusion induced acute kidney injury in rats. Application route and therapeutic window1. Acta Cir Bras 2019; 33:1016-1026. [PMID: 30517328 DOI: 10.1590/s0102-865020180110000008] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2018] [Accepted: 10/25/2018] [Indexed: 01/23/2023] Open
Abstract
PURPOSE To evaluate renal repair in rats who had renal infarction induced by the obstruction of blood flow in the renal artery and were treated with transplantation of adipose tissue derived mesenchymal stem cell. METHODS 16-week-old Wistar rats (n=72) were used, submitted to celiotomy and had of the renal artery and vein clipped for 24 hours. The animals were randomly assigned to 10 experimental homogeneous groups, corresponding to the treatments with phosphate-buffered saline (PBS) or adipose tissue derived mesenchymal stem cell (ADSC), duration of application (24 or 48 hours), and site of transplantation (lateral vein of the tail or intrarenal). After the treatments were performed, at 8 and 31 days, four animals in each group were subjected to left nephrectomy for histological studies. RESULTS Histologically, a higher amount of cell debris and tubules devoid of the epithelium and a higher degree of necrosis were observed in the groups treated with PBS, as opposed to a low degree of necrosis and higher tubular vascularization in the groups treated with ADSC, particularly in the group treated with intrarenal ADSC 48 hours after injury. CONCLUSION The transplantation of ADSC positively contributed to the replacement of necrotic tissue by renal tubular cells, vascularization of the renal parenchyma, and restoration of the organ function.
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Affiliation(s)
- Betânia Souza Monteiro
- Full Professor, Stem Cell and Cellular Therapy Laboratory, Animal Science Program, Universidade Vila Velha (UVV), Brazil. Conception and design of the study, manuscript writing, critical revision, final approval
| | - Bianka Souza Dos Santos
- Veterinary Medical, Stem Cell and Cellular Therapy Laboratory, Animal Science Program, UVV, Vila Velha-ES, Brazil. Technical procedures, acquisition of data, manuscript preparation and writing
| | - Bruna Lopes de Almeida
- Veterinary Medical, Stem Cell and Cellular Therapy Laboratory, Animal Science Program, UVV, Vila Velha-ES, Brazil. Technical procedures, acquisition of data, manuscript preparation and writing
| | - Emy Hiura
- Veterinary Medical, Stem Cell and Cellular Therapy Laboratory, Animal Science Program, UVV, Vila Velha-ES, Brazil. Technical procedures, acquisition of data, manuscript preparation and writing
| | - Wagner Alexey Back Fiorio
- Veterinay Medical, Advanced Imaging Center and Veterinary Pathology, Vila Velha-ES, Brazil. Histopathological examinations
| | - Gisele Pereira Valdetaro
- Veterinary Medical, Stem Cell and Cellular Therapy Laboratory, Animal Science Program, UVV, Vila Velha-ES, Brazil. Technical procedures, acquisition of data, manuscript preparation and writing
| | - Dariele Vieira Gonçalves
- Veterinary Medical, Stem Cell and Cellular Therapy Laboratory, Animal Science Program, UVV, Vila Velha-ES, Brazil. Technical procedures, acquisition of data, manuscript preparation and writing
| | - Caroline Saraiva Silva
- Veterinay Medical, PetScan Diagnoses Center, Vila Velha-ES, Brazil. Imagens examinations
| | - Tatiana Champion
- Assistant Professor, Veterinary Department, Universidade Federal da Fronteira Sul (UFFS), Realeza-PR, Brazil. Statistics analysis, critical revision, final approval
| | - Daniela Campagnol
- Veterinay Medical, Animal Experimentation Division, Clinical Hospital, Universidade Federal do Rio Grande do Sul (UFRS), Porto Alegre-RS, Brazil. Substantive scientific and intellectual contributions to the study, critical revision
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Mesenchymal stem cell-based drug delivery strategy: from cells to biomimetic. J Control Release 2018; 294:102-113. [PMID: 30553849 DOI: 10.1016/j.jconrel.2018.12.019] [Citation(s) in RCA: 190] [Impact Index Per Article: 27.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Revised: 12/11/2018] [Accepted: 12/12/2018] [Indexed: 12/13/2022]
Abstract
Owing to the diversity and ease of preparation of nanomaterials, the rational nanocarriers with a rational design have become increasingly popular in medical researches. Although nanoparticle-based drug delivery exhibits great potential, there are some challenges facing like rapid plasma clearance, triggering or aggravation of immune response, etc. Herein, cell-based targeted drug delivery systems have drawn more and more attention owing to low immunogenicity and intrinsic mutation rate, and innate ability to allow targeted delivery. Mesenchymal stem cells (MSCs) have been used in gene and drug delivery. The use of MSCs is a promising approach for the development of gene transfer systems and drug loading strategies because of their intrinsic properties, including homing ability and tumor tropism. By combining the inherent cell properties and merits of synthetic nanoparticles (NPs), cell membrane coated NPs emerge as the time requires. Overall, we provide a comprehensive overview of the utility of MSCs in drug and gene delivery as well as MSC membrane coated nanoparticles for therapy and drug delivery, aiming to figure out the significant room for development and highlight the potential future directions.
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43
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Xu Q, Zhang T, Wang Q, Jiang X, Li A, Li Y, Huang T, Li F, Hu Y, Ling D, Gao J. Uniformly sized iron oxide nanoparticles for efficient gene delivery to mesenchymal stem cells. Int J Pharm 2018; 552:443-452. [DOI: 10.1016/j.ijpharm.2018.10.023] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 09/28/2018] [Accepted: 10/08/2018] [Indexed: 12/18/2022]
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Wang X, Gao J, Ouyang X, Wang J, Sun X, Lv Y. Mesenchymal stem cells loaded with paclitaxel-poly(lactic- co-glycolic acid) nanoparticles for glioma-targeting therapy. Int J Nanomedicine 2018; 13:5231-5248. [PMID: 30237710 PMCID: PMC6136913 DOI: 10.2147/ijn.s167142] [Citation(s) in RCA: 94] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Background Mesenchymal stem cells (MSCs) possess inherent tropism towards tumor cells, and so have attracted increased attention as targeted-therapy vehicles for glioma treatment. Purpose The objective of this study was to demonstrate the injection of MSCs loaded with paclitaxel (Ptx)-encapsulated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for orthotopic glioma therapy in rats. Methods Ptx-PLGA NP-loaded MSC was obtained by incubating MSCs with Ptx-PLGA NPs. The drug transfer and cytotoxicity of Ptx-PLGA NP-loaded MSC against tumor cells were investigated in the transwell system. Biodistribution and antitumor activity was evaluated in the orthotopic glioma rats after contralateral injection. Results The optimal dose of MSC-loaded Ptx-PLGA NPs (1 pg/cell Ptx) had little effect on MSC-migration capacity, cell cycle, or multilineage-differentiation potential. Compared with Ptx-primed MSCs, Ptx-PLGA NP-primed MSCs had enhanced sustained Ptx release in the form of free Ptx and Ptx NPs. Ptx transfer from MSCs to glioma cells could induce tumor cell death in vitro. As for distribution in vivo, NP-loaded fluorescent MSCs were tracked throughout the tumor mass for 2 days after therapeutic injection. Survival was significantly longer after contralateral implantation of Ptx-PLGA NP-loaded MSCs than those injected with Ptx-primed MSCs or Ptx-PLGA NPs alone. Conclusion Based on timing and sufficient Ptx transfer from the MSCs to the tumor cells, Ptx-PLGA NP-loaded MSC is effective for glioma treatment. Incorporation of chemotherapeutic drug-loaded NPs into MSCs is a promising strategy for tumor-targeted therapy.
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Affiliation(s)
- Xiaoling Wang
- Department of Pharmacy, Zhejiang University City College, ;.,Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Jianqing Gao
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Xumei Ouyang
- Department of Pharmacy, Zhejiang University City College, ;.,Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Junbo Wang
- Department of Pharmacy, Zhejiang University City College,
| | - Xiaoyi Sun
- Department of Pharmacy, Zhejiang University City College,
| | - Yuanyuan Lv
- Department of Pharmacy, Zhejiang University City College,
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Marofi F, Vahedi G, Biglari A, Esmaeilzadeh A, Athari SS. Mesenchymal Stromal/Stem Cells: A New Era in the Cell-Based Targeted Gene Therapy of Cancer. Front Immunol 2017; 8:1770. [PMID: 29326689 PMCID: PMC5741703 DOI: 10.3389/fimmu.2017.01770] [Citation(s) in RCA: 100] [Impact Index Per Article: 12.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2017] [Accepted: 11/27/2017] [Indexed: 02/06/2023] Open
Abstract
In recent years, in light of the promising potentials of mesenchymal stromal/stem cells (MSCs) for carrying therapeutic anticancer genes, a complete revisitation on old chemotherapy-based paradigms has been established. This review attempted to bring forward and introduce the novel therapeutic opportunities of using genetically engineered MSCs. The simplicities and advantages of MSCs for medical applications make them a unique and promising option in the case of cancer therapy. Some of the superiorities of using MSCs as therapeutic gene micro-carriers are the easy cell-extraction procedures and their abundant proliferation capacity in vitro without losing their main biological properties. Targeted therapy by using MSCs as the delivery vehicles of therapeutic genes is a new approach in the treatment of various types of cancers. Some of the distinct properties of MSCs, such as tumor-tropism, non-immunogenicity, stimulatory effect on the anti-inflammatory molecules, inhibitory effect on inflammatory responses, non-toxicity against the normal tissues, and easy processes for the clinical use, have formed the basis of attention to MSCs. They can be easily used for the treatment of damaged or injured tissues, regenerative medicine, and immune disorders. This review focused on the drugability of MSCs and their potential for the delivery of candidate anticancer genes. It also briefly reviewed the vectors and methods used for MSC-mediated gene therapy of malignancies. Also, the challenges, limitations, and considerations in using MSCs for gene therapy of cancer and the new methods developed for resolution of these problems are reviewed.
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Affiliation(s)
- Faroogh Marofi
- Department of Hematology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ghasem Vahedi
- Research Center for Food Hygiene and Safety, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Alireza Biglari
- Department of Genetics and Molecular Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Abdolreza Esmaeilzadeh
- Department of Immunology, Zanjan University of Medical Sciences, Zanjan, Iran.,Cancer Gene Therapy Research Center, Zanjan University of Medical Sciences, Zanjan, Iran
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Dapkute D, Steponkiene S, Bulotiene D, Saulite L, Riekstina U, Rotomskis R. Skin-derived mesenchymal stem cells as quantum dot vehicles to tumors. Int J Nanomedicine 2017; 12:8129-8142. [PMID: 29158674 PMCID: PMC5683786 DOI: 10.2147/ijn.s143367] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Purpose Cell-mediated delivery of nanoparticles is emerging as a new method of cancer diagnostics and treatment. Due to their inherent regenerative properties, adult mesenchymal stem cells (MSCs) are naturally attracted to wounds and sites of inflammation, as well as tumors. Such characteristics enable MSCs to be used in cellular hitchhiking of nanoparticles. In this study, MSCs extracted from the skin connective tissue were investigated as transporters of semiconductor nanocrystals quantum dots (QDs). Materials and methods Cytotoxicity of carboxylated CdSe/ZnS QDs was assessed by lactate dehydrogenase cell viability assay. Quantitative uptake of QDs was determined by flow cytometry; their intracellular localization was evaluated by confocal microscopy. In vitro tumor-tropic migration of skin-derived MSCs was verified by Transwell migration assay. For in vivo migration studies of QD-loaded MSCs, human breast tumor-bearing immunodeficient mice were used. Results QDs were found to be nontoxic to MSCs in concentrations no more than 16 nM. The uptake studies showed a rapid QD endocytosis followed by saturating effects after 6 h of incubation and intracellular localization in the perinuclear region. In vitro migration of MSCs toward MDA-MB-231 breast cancer cells and their conditioned medium was up to nine times greater than the migration toward noncancerous breast epithelial cells MCF-10A. In vivo, systemically administered QD-labeled MSCs were mainly located in the tumor and metastatic tissues, evading most healthy organs with the exception being blood clearance organs (spleen, kidneys, liver). Conclusion Skin-derived MSCs demonstrate applicability in cell-mediated delivery of nanoparticles. The findings presented in this study promise further development of a cell therapy and nanotechnology-based tool for early cancer diagnostics and therapy.
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Affiliation(s)
- Dominyka Dapkute
- Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania.,Institute of Biosciences, Vilnius University, Vilnius, Lithuania
| | - Simona Steponkiene
- Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania
| | - Danute Bulotiene
- Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania
| | - Liga Saulite
- Faculty of Medicine, University of Latvia, Riga, Latvia
| | - Una Riekstina
- Faculty of Medicine, University of Latvia, Riga, Latvia
| | - Ricardas Rotomskis
- Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania.,Biophotonics Group of Laser Research Center, Faculty of Physics, Vilnius University, Vilnius, Lithuania
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47
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Moradian Tehrani R, Verdi J, Noureddini M, Salehi R, Salarinia R, Mosalaei M, Simonian M, Alani B, Ghiasi MR, Jaafari MR, Mirzaei HR, Mirzaei H. Mesenchymal stem cells: A new platform for targeting suicide genes in cancer. J Cell Physiol 2017; 233:3831-3845. [DOI: 10.1002/jcp.26094] [Citation(s) in RCA: 51] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2017] [Accepted: 07/11/2017] [Indexed: 12/30/2022]
Affiliation(s)
- Rana Moradian Tehrani
- Department of Applied Cell SciencesSchool of Medicine, Kashan University of Medical SciencesKashanIran
| | - Javad Verdi
- Department of Applied Cell SciencesSchool of Medicine, Kashan University of Medical SciencesKashanIran
- Department of Applied Cell Sciences School of Advanced Technologies in Medicine, Tehran University of Medical SciencesTehranIran
| | - Mahdi Noureddini
- Department of Applied Cell SciencesSchool of Medicine, Kashan University of Medical SciencesKashanIran
| | - Rasoul Salehi
- Department of Genetic and Molecular BiologyIsfahan University of Medical SciencesIsfahanIran
| | - Reza Salarinia
- Department of Medical Biotechnology and Molecular SciencesSchool of MedicineNorth Khorasan University of Medical SciencesBojnurdIran
| | - Meysam Mosalaei
- Department of Genetic and Molecular BiologyIsfahan University of Medical SciencesIsfahanIran
| | - Miganosh Simonian
- Department of Genetic and Molecular BiologyIsfahan University of Medical SciencesIsfahanIran
| | - Behrang Alani
- Department of Applied Cell SciencesSchool of Medicine, Kashan University of Medical SciencesKashanIran
| | - Moosa Rahimi Ghiasi
- Department of Genetic and Molecular BiologyIsfahan University of Medical SciencesIsfahanIran
| | - Mahmoud Reza Jaafari
- School of PharmacyNanotechnology Research CenterMashhad University of Medical SciencesMashhadIran
| | - Hamed Reza Mirzaei
- Department of Clinical Laboratory SciencesSchool of Allied Medical SciencesKashan University of Medical SciencesKashanIran
- Department of Immunology, School of MedicineTehran University of Medical SciencesTehranIran
- Clinical Research DivisionFred Hutchinson Cancer Research CenterSeattleWashington
| | - Hamed Mirzaei
- Department of Medical Biotechnology, School of MedicineMashhad University of Medical SciencesMashhadIran
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Kucerova L, Durinikova E, Toro L, Cihova M, Miklikova S, Poturnajova M, Kozovska Z, Matuskova M. Targeted antitumor therapy mediated by prodrug-activating mesenchymal stromal cells. Cancer Lett 2017; 408:1-9. [PMID: 28838843 DOI: 10.1016/j.canlet.2017.08.016] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 08/09/2017] [Accepted: 08/11/2017] [Indexed: 12/14/2022]
Abstract
Mesenchymal stromal cells (MSCs) were introduced as tumor-targeted vehicles suitable for delivery of the gene-directed enzyme/prodrug therapy more than 10 years ago. Over these years key properties of tumor cells and MSCs, which are crucial for the treatment efficiency, were examined; and there are some critical issues to be considered for the maximum antitumor effect. Moreover, engineered MSCs expressing enzymes capable of activating non-toxic prodrugs achieved long-term curative effect even in metastatic and hard-to-treat tumor types in pre-clinical scenario(s). These gene-modified MSCs are termed prodrug-activating MSCs throughout the text and represent promising approach for further clinical application. This review summarizes major determinants to be considered for the application of the prodrug-activating MSCs in antitumor therapy in order to maximize therapeutic efficiency.
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Affiliation(s)
- Lucia Kucerova
- Laboratory of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia.
| | - Erika Durinikova
- Laboratory of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
| | - Lenka Toro
- Laboratory of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
| | - Marina Cihova
- Laboratory of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
| | - Svetlana Miklikova
- Laboratory of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
| | - Martina Poturnajova
- Laboratory of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
| | - Zuzana Kozovska
- Laboratory of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
| | - Miroslava Matuskova
- Laboratory of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dubravska cesta 9, 845 05 Bratislava, Slovakia
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Huang B, Jiang XC, Zhang TY, Hu YL, Tabata Y, Chen Z, Pluchino S, Gao JQ. Peptide modified mesenchymal stem cells as targeting delivery system transfected with miR-133b for the treatment of cerebral ischemia. Int J Pharm 2017; 531:90-100. [PMID: 28827201 DOI: 10.1016/j.ijpharm.2017.08.073] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2017] [Revised: 07/12/2017] [Accepted: 08/12/2017] [Indexed: 12/13/2022]
Abstract
Mesenchymal stem cells (MSCs) have been regarded as potential targeting vehicles and demonstrated to exert therapeutic benefits for brain diseases. Direct homing to diseased tissue is crucial for stem cell-based therapy. In this study, a peptide-based targeting approach was established to enhance cell homing to cerebral ischemic lesion. Palmitic acid-peptide painted onto the cell membrane was able to direct MSCs to ischemic tissues without any observed cell cytotoxicity and influence on differentiation, thus reducing accumulation of cells in peripheral organs and increasing engraftment of cells in the targeted tissues. With enhanced cell homing, MSCs were used to deliver miR-133b to increase the expression level of miR-133b in an ischemic lesion and further improve therapeutic effects. This study is the first to develop MSCs co-modified with targeting peptide and microRNAs as potential targeting therapeutic agents. This targeting delivery system is expected to be applicable to other cell types and other diseases aside from stroke.
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Affiliation(s)
- Bing Huang
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, PR China
| | - Xin-Chi Jiang
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, PR China
| | - Tian-Yuan Zhang
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, PR China
| | - Yu-Lan Hu
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, PR China
| | - Yasuhiko Tabata
- Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
| | - Zhong Chen
- Department of Pharmacology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, PR China
| | - Stefano Pluchino
- Department of Clinical Neurosciences, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridgeshire, UK
| | - Jian-Qing Gao
- Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, PR China; Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cell and Regenerative Medicine, Zhejiang University, Hangzhou, Zhejiang, PR China.
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50
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Dash TK, Konkimalla VB. Formulation and Optimization of Doxorubicin and Biochanin A Combinational Liposomes for Reversal of Chemoresistance. AAPS PharmSciTech 2017; 18:1116-1124. [PMID: 27600324 DOI: 10.1208/s12249-016-0614-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2016] [Accepted: 08/09/2016] [Indexed: 01/09/2023] Open
Abstract
Circumvention of drug resistance still remains a challenge in the development of anticancer therapeutics. Combinational nano-formulations provide many avenues for effective cancer therapy and reversal of drug resistance. In the current study, combination of biochanin A (BioA) and doxorubicin (DOX) in liposomes were prepared and studied for its potential to reverse DOX resistance in COLO205 cells. After development and validation of DOX resistant cells of COLO205 (ColoR), dosing ratio of DOX and BioA for reversal of DOX resistance was determined by co-treatment in ColoR cells. As limited solubility and analytical data available for BioA, therefore solubility was studied for BioA and analytical method was developed for the combination. Combinational liposomes were prepared and optimized for both lipid content and surface charge by evaluating size, polydispersity index, zeta potential, and encapsulation efficiency. The optimized formulation had a size about 125 nm; zeta potential of -19.5 mV and 70% encapsulation efficiency (EE) for BioA. Thus, prepared combinational liposomes of DOX and BioA were evaluated for its cellular uptake and efficacy to reverse DOX resistance. From the study, increased DOX uptake and promising effect for reversal of DOX resistance was observed.
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